TY - JOUR AB - OBJECTIVE: Here, we aimed to investigate the role of glucocorticoid and mineralocorticoid receptors (GRs and MRs, respectively) in the regulation of energy homeostasis. METHODS: We used three mouse models with simultaneous deletion of GRs and MRs in either forebrain neurons, the paraventricular nucleus, or corticotropin-releasing hormone (CRH) neurons and compared them with wild-type controls or isolated knockout groups. In addition to body weight, food intake, energy expenditure, insulin sensitivity, fat/lean mass distribution, and plasma corticosterone levels, we also performed transcriptomic analysis of CRH neurons and assessed their response to melanocortinergic stimulation. RESULTS: Similar to global double-knockout models, deletion of GRs and MRs specifically in mature CRH neurons resulted in obesity. Importantly, the latter was accompanied by insulin resistance, but not increased plasma corticosterone levels. Transcriptomic analysis of these neurons revealed upregulation of several genes involved in postsynaptic signal transduction, including the Ptk2b gene, which encodes proline-rich tyrosine kinase 2. Knockout of both nuclear receptors leads to upregulation of Ptk2b in CRH neurons, which results in their diminished responsiveness to melanocortinergic stimulation. CONCLUSIONS: Our data demonstrate the functional redundancy of GRs and MRs in CRH neurons to maintain energy homeostasis and prevent obesity. Simultaneous targeting of both receptors might represent an unprecedented approach to counteract obesity. AU - Liu, Y.* AU - Lin, D.* AU - Najam, S.S.* AU - Huang, S.* AU - Song, M.* AU - Sirakawin, C.* AU - Zhao, C.* AU - Jiang, H.* AU - Konopka, W.* AU - Herzig, S. AU - Vinnikov, I.A.* C1 - 71808 C2 - 56435 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 1885-1896 TI - Functional redundancy between glucocorticoid and mineralocorticoid receptors in mature corticotropin-releasing hormone neurons protects from obesity. JO - Obesity VL - 32 IS - 10 PB - Wiley PY - 2024 SN - 1930-7381 ER - TY - JOUR AB - Objective: The aim of this study was to discover novel markers underlying the improvement of skeletal muscle metabolism after bariatric surgery. Methods: Skeletal muscle transcriptome data of lean people and people with obesity, before and 1 year after bariatric surgery, were subjected to weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression. Results of LASSO were confirmed in a replication cohort. Results: The expression levels of 440 genes differing between individuals with and without obesity were no longer different 1 year after surgery, indicating restoration. WGCNA clustered 116 genes with normalized expression in one major module, particularly correlating to weight loss and decreased plasma free fatty acids (FFA), 44 of which showed an obesity-related phenotype upon deletion in mice. Among the genes of the major module, 105 represented prominent markers for reduced FFA concentration, including 55 marker genes for decreased BMI in both the discovery and replication cohorts. Conclusions: Previously unknown gene networks and marker genes underlined the important role of FFA in restoring muscle gene expression after bariatric surgery and further suggest novel therapeutic targets for obesity. AU - Ouni, M.* AU - Kovác, L.* AU - Gancheva, S.* AU - Jähnert, M.* AU - Zuljan, E.* AU - Gottmann, P.* AU - Kahl, S.* AU - Hrabě de Angelis, M. AU - Roden, M.* AU - Schürmann, A.* C1 - 68955 C2 - 53756 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 363-375 TI - Novel markers and networks related to restored skeletal muscle transcriptome after bariatric surgery. JO - Obesity VL - 32 IS - 2 PB - Wiley PY - 2024 SN - 1930-7381 ER - TY - JOUR AB - OBJECTIVE: This study aimed to identify sleep clusters based on objective multidimensional sleep characteristics and test their associations with adolescent cardiometabolic health. METHODS: The authors included 1090 participants aged 14.3 to 16.4 years (mean = 15.2 years) who wore 7-day accelerometers during the 15-year follow-up of the German Infant Study on the influence of Nutrition Intervention PLUS environmental and genetic influences on allergy development (GINIplus) and the Influence of Lifestyle factors on the development of the Immune System and Allergies in East and West Germany (LISA) birth cohorts. K-means cluster analysis was performed across 12 sleep characteristics reflecting sleep quantity, quality, schedule, variability, and regularity. Cardiometabolic risk factors included fat mass index (FMI), blood pressure, triglycerides, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and insulin resistance (n = 505). Linear and logistic regression models were examined. RESULTS: Five sleep clusters were identified: good sleep (n = 337); delayed sleep phase (n = 244); sleep irregularity and variability (n = 108); fragmented sleep (n = 313); and prolonged sleep latency (n = 88). The "prolonged sleep latency" cluster was associated with increased sex-scaled FMI (β = 0.39, 95% confidence interval: 0.15-0.62) compared with the "good sleep" cluster. The "sleep irregularity and variability" cluster was associated with increased odds of high triglycerides only in male individuals (odds ratio: 9.50, 95% confidence interval: 3.22-28.07), but this finding was not confirmed in linear models. CONCLUSIONS: The prolonged sleep latency cluster was associated with higher FMI in adolescents, whereas the sleep irregularity and variability cluster was specifically linked to elevated triglycerides (≥1.7 mmol/L) in male individuals. AU - Wang, M. AU - Flexeder, C. AU - Harris, C. AU - Thiering, E. AU - Koletzko, S.* AU - Bauer, C.P.* AU - Schulte-Körne, G.* AU - von Berg, A.* AU - Berdel, D.* AU - Heinrich, J.* AU - Schulz, H. AU - Schikowski, T.* AU - Peters, A. AU - Standl, M. C1 - 68705 C2 - 54914 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 200-213 TI - Accelerometry-assessed sleep clusters and cardiometabolic risk factors in adolescents. JO - Obesity VL - 32 IS - 1 PB - Wiley PY - 2024 SN - 1930-7381 ER - TY - JOUR AB - OBJECTIVE: Induction of browning in white adipose tissue (WAT) increases energy expenditure and may be an attractive target for the treatment of obesity. Since activation of Fas (CD95) induces pathways known to blunt expression of uncoupling protein 1 (UCP1), we hypothesized that Fas expression in adipocytes inhibits WAT browning and thus contributes to the development of obesity. METHODS: Adipocyte-specific Fas knockout (FasΔadipo) and control littermate (FasF/F) mice were fed a regular chow diet or a high-fat diet (HFD) for 20 weeks. Energy expenditure was assessed by indirect calorimetry, and browning was determined in subcutaneous WAT. In vitro, UCP1 was analyzed in subcutaneous murine adipocytes treated with or without Fas ligand. Moreover, FAS expression in WAT was correlated to UCP1 and percentage of body fat in human individuals. RESULTS: HFD-fed FasΔadipo mice displayed reduced body weight gain and blunted adiposity compared to control littermates. Concomitantly, whole-body energy expenditure and WAT browning were elevated. In cultured adipocytes, Fas ligand treatment blunted isoproterenol-induced UCP1 protein levels. In support of these findings in rodents, FAS expression in WAT correlated negatively with UCP1 but positively with adiposity in human individuals. CONCLUSIONS: Fas activation in adipocytes contributes to HFD-associated adiposity in rodents and may be a therapeutic target to reduce obesity and associated diseases. AU - Wueest, S.* AU - Scaffidi, C.* AU - van Krieken, P.P.* AU - Konrad, N.K.* AU - Koch, C.* AU - Wiedemann, M.S.F.* AU - Goergen, A.* AU - Borsigova, M.* AU - Lempesis, I.G.* AU - Fullin, J.* AU - Manolopoulos, K.N.* AU - Böttcher, S.* AU - Goossens, G.H.* AU - Blüher, M. AU - Konrad, D.* C1 - 71209 C2 - 56008 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Fas (CD95) expression in adipocytes contributes to diet-induced obesity. JO - Obesity PB - Wiley PY - 2024 SN - 1930-7381 ER - TY - JOUR AB - OBJECTIVE: The objective of this study was to explore the effects of a green Mediterranean (green-MED) diet, which is high in dietary polyphenols and green plant-based protein and low in red/processed meat, on cardiovascular disease and inflammation-related circulating proteins and their associations with cardiometabolic risk parameters. METHODS: In the 18-month weight loss trial Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS), 294 participants with abdominal obesity were randomized to basic healthy dietary guidelines, Mediterranean (MED), or green-MED diets. Both isocaloric MED diet groups consumed walnuts (28 g/day), and the green-MED diet group also consumed green tea (3-4 cups/day) and green shakes (Mankai plant shake, 500 mL/day) and avoided red/processed meat. Proteome panels were measured at three time points using Olink CVDII. RESULTS: At baseline, a dominant protein cluster was significantly related to higher phenotypic cardiometabolic risk parameters, with the strongest associations attributed to magnetic resonance imaging-assessed visceral adiposity (false discovery rate of 5%). Overall, after 6 months of intervention, both the MED and green-MED diets induced improvements in cardiovascular disease and proinflammatory risk proteins (p < 0.05, vs. healthy dietary guidelines), with the green-MED diet leading to more pronounced beneficial changes, largely driven by dominant proinflammatory proteins (IL-1 receptor antagonist protein, IL-16, IL-18, thrombospondin-2, leptin, prostasin, galectin-9, and fibroblast growth factor 21; adjusted for age, sex, and weight loss; p < 0.05). After 18 months, proteomics cluster changes presented the strongest correlations with visceral adiposity reduction. CONCLUSIONS: Proteomics clusters may enhance our understanding of the favorable effect of a green-MED diet that is enriched with polyphenols and low in red/processed meat on visceral adiposity and cardiometabolic risk. AU - Zelicha, H.* AU - Kaplan, A.* AU - Yaskolka Meir, A.* AU - Rinott, E.* AU - Tsaban, G.* AU - Blüher, M. AU - Klöting, N. AU - Ceglarek, U.* AU - Isermann, B.* AU - Stumvoll, M.* AU - Chassidim, Y.* AU - Shelef, I.* AU - Hu, F.B.* AU - Shai, I.* C1 - 70695 C2 - 55816 CY - 111 River St, Hoboken 07030-5774, Nj Usa TI - Altered proteome profiles related to visceral adiposity may mediate the favorable effect of green Mediterranean diet: The DIRECT-PLUS trial. JO - Obesity PB - Wiley PY - 2024 SN - 1930-7381 ER - TY - JOUR AB - Objective: Vaspin (visceral adipose tissue derived serine protease inhibitor, SERPINA12) is associated with obesity-related metabolic traits, but its causative role is still elusive. The role of genetics in serum vaspin variability to establish its causal relationship with metabolically relevant traits was investigated. Methods: A meta-analysis of genome-wide association studies for serum vaspin from six independent cohorts (N = 7446) was conducted. Potential functional variants of vaspin were included in Mendelian randomization (MR) analyses to assess possible causal pathways between vaspin and homeostasis model assessment and lipid traits. To further validate the MR analyses, data from Genotype-Tissue Expression (GTEx) were analyzed, db/db mice were treated with vaspin, and serum lipids were measured. Results: A total of 468 genetic variants represented by five independent variants (rs7141073, rs1956709, rs4905216, rs61978267, rs73338689) within the vaspin locus were associated with serum vaspin (all p < 5×10−8, explained variance 16.8%). MR analyses revealed causal relationships between serum vaspin and triglycerides, low-density lipoprotein, and total cholesterol. Gene expression correlation analyses suggested that genes, highly correlated with vaspin expression in adipose tissue, are enriched in lipid metabolic processes. Finally, in vivo vaspin treatment reduced serum triglycerides in obese db/db mice. Conclusions: The data show that serum vaspin is strongly determined by genetic variants within vaspin, which further highlight vaspin's causal role in lipid metabolism. AU - Breitfeld, J.* AU - Horn, K.* AU - Le Duc, D.* AU - Velluva, A.* AU - Marzi, C. AU - Grallert, H. AU - Friedrich, N.* AU - Pietzner, M.* AU - Völker, U.* AU - Völzke, H.* AU - Ahlqvist, E.* AU - Aly, D.M.* AU - Tuomi, T.* AU - Baber, R.* AU - Kratzsch, J.* AU - Thiery, J.* AU - Isermann, B.* AU - Loeffler, M.* AU - Klöting, N. AU - Blüher, M. AU - Stumvoll, M. AU - Heiker, J.T. AU - Tönjes, A.* AU - Scholz, M.* AU - Kovacs, P.* C1 - 68236 C2 - 54837 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 2862-2874 TI - Genetic dissection of serum vaspin highlights its causal role in lipid metabolism. JO - Obesity VL - 31 IS - 11 PB - Wiley PY - 2023 SN - 1930-7381 ER - TY - JOUR AB - OBJECTIVE: The aim of this study was to examine how improvement in BMI with the glucagon-like peptide-1 receptor agonist semaglutide translated to changes in BMI category in a post hoc analysis of the double-blind, phase 3a randomized controlled Semaglutide Treatment Effect in People with obesity (STEP) TEENS trial. METHODS: Adolescents with obesity received once-weekly subcutaneous semaglutide 2.4 mg or placebo plus lifestyle intervention, which comprised counseling in healthy nutrition and a goal of 60 minutes of moderate- to high-intensity physical activity per day. Achievement of an improvement in BMI category and attainment of normal-weight or overweight BMI by week 68 were analyzed using logistic regression models. RESULTS: In the overall population, 44.9% of participants receiving semaglutide achieved weight reduction resulting in reclassification to a normal-weight or overweight BMI category versus 12.1% receiving placebo at week 68 (odds ratio: 22.7; 95% CI: 7.6-67.9). The proportion of semaglutide-treated participants in obesity class III decreased from 37.3% to 13.6% but increased with placebo. The odds ratio for achieving an improvement of at least one BMI category was significantly greater with semaglutide versus placebo (23.5; 95% CI: 9.9-55.5); an improvement of at least one BMI category was seen in 73.7% of participants receiving semaglutide compared with 19.0% of participants receiving placebo. CONCLUSIONS: Semaglutide was highly effective in reducing BMI category. While on treatment, most trial participants' BMI improved by at least one category, and >40% reached a category below the obesity threshold. AU - Kelly, A.S.* AU - Arslanian, S.* AU - Hesse, D.* AU - Iversen, A.T.* AU - Körner, A. AU - Schmidt, S.* AU - Sørrig, R.* AU - Weghuber, D.* AU - Jastreboff, A.M.* C1 - 67927 C2 - 54405 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 2139-2149 TI - Reducing BMI below the obesity threshold in adolescents treated with once-weekly subcutaneous semaglutide 2.4 mg. JO - Obesity VL - 31 IS - 8 PB - Wiley PY - 2023 SN - 1930-7381 ER - TY - JOUR AB - Objective: In obesity, adipocyte hypertrophy is detrimental to health, but its' interrelation with fibrosis in the visceral adipose tissue (VAT) depot remains unclear. Because VAT is less accessible via biopsy, biomarkers for VAT quality are needed. The authors hypothesized that VAT adipocyte size and fibrosis are interrelated and can be estimated by circulating microRNAs (circ-miRNAs), contributing to subphenotyping obesity. Methods: Adipocyte size and AT fibrosis were estimated in n = 43 participants (BMI ≥ 30 kg/m2). Circ-miRNAs were sequenced (Next Generation Sequencing). Results: Participants with above- versus below-median VAT adipocyte area exhibited metabolic dysfunction but lower total and pericellular fibrosis. VAT adipocyte size remained associated with metabolic dysfunction even when controlling for BMI or VAT fibrosis in the entire cohort, as in matched-pairs subanalyses. Next Generation Sequencing uncovered 22 and 6 circ-miRNAs associated with VAT adipocyte size and fibrosis, respectively, with miRNA-130b-3p common to both analyses. The combination of miRNA-130b-3p + miR-150-5p + high-density lipoprotein cholesterol discriminated among those with large versus small VAT adipocytes (receiver operating characteristic-area under the curve: 0.872 [95% CI: 0.747–0.996]), whereas miRNA-130b-3p + miRNA-15a-5p + high-density lipoprotein cholesterol discriminated among those with low and high fibrosis (receiver operating characteristic-area under the curve: 0.823 [95% CI: 0.676–0.97]). Conclusions: These findings suggest that VAT adipocyte size and fibrosis are inversely correlated in obesity and can be estimated by distinct circ-miRNAs, providing a potential tool to subphenotype obesity via a liquid biopsy-like approach to assess VAT health in nonsurgical patients. AU - Pincu, Y.* AU - Makarenkov, N.* AU - Tsitrina, A.A.* AU - Rosengarten-Levine, M.* AU - Haim, Y.* AU - Yoel, U.* AU - Liberty, I.F.* AU - Dukhno, O.* AU - Kukeev, I.* AU - Blüher, M. AU - Veksler-Lublinsky, I.* AU - Rudich, A.* C1 - 68201 C2 - 54844 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 2986-2997 TI - Visceral adipocyte size links obesity with dysmetabolism more than fibrosis, and both can be estimated by circulating miRNAs. JO - Obesity VL - 31 IS - 12 PB - Wiley PY - 2023 SN - 1930-7381 ER - TY - JOUR AB - OBJECTIVE: The first-line approach for childhood obesity is lifestyle intervention (LI); however, success varies. This study aimed first to identify distinct subgroups of response in children living with overweight and obesity and second to elucidate predictors for subclusters. METHODS: Based on the obesity patient follow-up registry the APV (Adipositas-Patienten-Verlaufsdokumentation) initiative, a total of 12,453 children and adolescents (median age: 11.5 [IQR: 9.7-13.2] years; BMI z score [BMIz]: 2.06 [IQR: 1.79-2.34]; 52.6% girls) living with overweight/obesity and participating in outpatient LI were studied. Longitudinal k-means clustering was used to identify individual BMIz response curve for up to 2 years after treatment initiation. Multinomial logistic regression was used to elucidate predictors for cluster membership. RESULTS: A total of 36.3% of children and adolescents experienced "no BMIz loss." The largest subcluster (44.8%) achieved "moderate BMIz loss," with an average delta-BMIz of -0.23 (IQR: -0.33 to -0.14) at study end. A total of 18.9% had a "pronounced BMIz loss" up to -0.61 (IQR: -0.76 to -0.49). Younger age and lower BMIz at LI initiation, larger initial BMIz loss, and less social deprivation were linked with higher likelihood for moderate or pronounced BMIz loss compared with the no BMIz loss cluster (all p < 0.05). CONCLUSIONS: These results support the importance of patient-tailored intervention and earlier treatment escalation in high-risk individuals who have little chance of success. AU - Prinz, N.* AU - Pomares-Millan, H.* AU - Dannemann, A.* AU - Giordano, G.N.* AU - Joisten, C.* AU - Körner, A. AU - Weghuber, D.* AU - Weihrauch-Blüher, S.* AU - Wiegand, S.* AU - Holl, R.W.* AU - Lanzinger, S.* C1 - 68031 C2 - 54509 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 2375-2385 TI - Who benefits most from outpatient lifestyle intervention? An IMI-SOPHIA study on pediatric individuals living with overweight and obesity. JO - Obesity VL - 31 IS - 9 PB - Wiley PY - 2023 SN - 1930-7381 ER - TY - JOUR AB - OBJECTIVE: Dysregulated body fat distribution is a major determinant of various diseases. In particular, increased visceral fat mass and ectopic lipids in the liver are linked to metabolic disorders such as insulin resistance and type 2 diabetes. Furthermore, interscapular fat is considered to be a metabolically active fat compartment. METHODS: This study measured interscapular fat mass and investigated its relationship with glucose metabolism in 822 individuals with a wide range of BMI values and different glucose tolerance statuses. Magnetic resonance imaging was used to quantify body fat depots, and an oral glucose tolerance test was performed to determine glucose metabolism. RESULTS: Elevated interscapular fat mass was positively associated with age, BMI, and total body, visceral, and subcutaneous adipose tissue mass. High interscapular fat mass associated with elevated fasting glucose levels, glucose levels at 2 hours during the oral glucose tolerance test, glycated hemoglobin, and insulin resistance, independent of sex, age, and total body and visceral fat mass. CONCLUSIONS: In conclusion, interscapular fat might be a highly specific fat compartment with a potential impact on glucose metabolism and the pathogenesis of diabetes mellitus. AU - Vosseler, A. AU - Machann, J. AU - Fritsche, L. AU - Prystupa, K. AU - Kübler, C. AU - Häring, H.-U. AU - Birkenfeld, A.L. AU - Stefan, N. AU - Peter, A. AU - Fritsche, A. AU - Wagner, R. AU - Heni, M. C1 - 66357 C2 - 52802 SP - 2233-2241 TI - Interscapular fat is associated with impaired glucose tolerance and insulin resistance independent of visceral fat mass. JO - Obesity VL - 30 IS - 11 PY - 2022 SN - 1930-7381 ER - TY - JOUR AU - Klöting, N. AU - Ristow, M.* AU - Blüher, M. C1 - 60357 C2 - 49695 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 2266-2267 TI - Effects of exercise on ACE2. JO - Obesity VL - 28 IS - 12 PB - Wiley PY - 2020 SN - 1930-7381 ER - TY - JOUR AB - Objective: Prepregnancy obesity and extensive weight gain can lead to diseases in the offspring later in life. The aim of this study was to evaluate the effect of anthropometric and metabolic factors on the fetal autonomic nervous system (ANS) in uncomplicated pregnancies. Methods: A total of 184 pregnant women in the second or third trimester were included, and for 104 women, maternal insulin sensitivity (ISI) was determined. Fetal heart rate (HR) and heart rate variability (HRV) were determined by magnetic recording. Associations of maternal prepregnancy BMI, weight gain, and ISI with fetal HR and HRV were evaluated by ANCOVA, partial correlation, and mediation analysis. Results: HR was increased and HRV decreased in fetuses of mothers with overweight or obesity in comparison to normal-weight mothers. Fetal HR was negatively correlated with maternal weight gain. Maternal prepregnancy BMI was positively correlated with fetal high frequency and was negatively correlated with low frequency and low/high frequency ratio. Maternal ISI showed a negative correlation with fetal HR. Conclusions: The results show that the fetal ANS is sensitive to alterations of prepregnancy BMI, weight changes, and glucose metabolism. These findings highlight the importance of the intrauterine environment on the developing ANS and the possible programming of obesity. AU - Mat-Husin, H. AU - Schleger, F. AU - Bauer, I. AU - Fehlert, E.* AU - Kiefer-Schmidt, I.* AU - Weiss, M.* AU - Kagan, K.O.* AU - Brucker, S.* AU - Pauluschke-Fröhlich, J.* AU - Eswaran, H.* AU - Häring, H.-U. AU - Fritsche, A. AU - Preissl, H. C1 - 57694 C2 - 48001 SP - 114-121 TI - Maternal weight, weight gain and metabolism are associated with changes in fetal heart rate and variabilit. JO - Obesity VL - 28 IS - 1 PY - 2020 SN - 1930-7381 ER - TY - JOUR AB - Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS) Objective: People with diabetes show great variability in weight gain and duration of obesity at the time of diagnosis. BMI trajectories and other cardiometabolic risk factors prior to type 2 diabetes were investigated. Methods: A total of 6,223 participants from the Rotterdam Study cohort were included. BMI patterns before diagnosis of diabetes were identified through latent class trajectories. Results: During a mean follow-up of 13.7 years, 565 participants developed type 2 diabetes. Three distinct trajectories of BMI were identified, including the “progressive overweight” group (n = 481, 85.1%), “progressive weight loss” group (n = 59, 10.4%), and “persistently high BMI” group (n = 25, 4.4%). The majority, the progressive overweight group, was characterized by a steady increase of BMI in the overweight range 10 years before diabetes diagnosis. The progressive weight loss group had fluctuations of glucose and marked beta cell function loss. The persistently high BMI group was characterized by a slight increase in insulin levels and sharp increase of insulin resistance accompanied by a rapid decrease of beta cell function. Conclusions : Heterogeneity of BMI changes prior to type 2 diabetes was found in a middle-aged and elderly white population. Prevention strategies should be tailored rather than focusing only on high-risk individuals. AU - Nano, J. AU - Dhana, K.* AU - Asllanaj, E.* AU - Sijbrands, E.* AU - Ikram, M.A.* AU - Dehghan, A.* AU - Muka, T.* AU - Franco, O.H.* C1 - 59056 C2 - 48548 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 1149-1156 TI - Trajectories of BMI before diagnosis of type 2 diabetes: The Rotterdam study. JO - Obesity VL - 28 IS - 6 PB - Wiley PY - 2020 SN - 1930-7381 ER - TY - JOUR AB - Objective This study assessed the changes in red blood cell total phospholipid (RBC-TPL) and subcutaneous adipose tissue (SAT) fatty acid (FA) composition in response to 12 weeks of exercise training in South African women with obesity and the associations with changes in cardiometabolic risk factors. Methods Previously sedentary women were randomized into control (n = 15) or exercise (n = 20) groups. RBC-TPL and SAT FA profiles, SAT gene expression, systemic inflammatory markers, liver fat, and insulin sensitivity (S-I) were measured before and after the intervention. Results Compared with control, exercise training induced decreases in RBC-TPL dihomo-gamma-linolenic acid content and stearoyl-CoA desaturase-1 and increased delta-5 desaturase-estimated activity (P < 0.05). In the combined group, these changes correlated with changes in circulating leptin and TNF alpha (P < 0.05), as well as lower liver fat (P < 0.01). Exercise training decreased saturated FA (lauric and myristic acids) and increased polyunsaturated FA (eicosadienoic and adrenic acids) (P < 0.05) in abdominal SAT, whereas gamma-linolenic acid decreased (P < 0.01) in gluteal SAT. These changes in RBC-TPL and SAT FA compositions were not associated with changes in SAT gene expression and S-I. Conclusions Exercise training alters RBC-TPL desaturase activities, which correlate with lower liver fat and systemic inflammation but not with the improvement of S-I. AU - Nono Nankam, P.A.* AU - Mendham, A.E.* AU - van Jaarsveld, P.J.* AU - Adams, K.* AU - Fortuin-de Smidt, M.C.* AU - Clamp, L.* AU - Blüher, M. AU - Goedecke, J.H.* C1 - 59601 C2 - 48867 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 1456-1466 TI - Exercise training alters red blood cell fatty acid desaturase indices and adipose tissue fatty acid profile in African women with obesity. JO - Obesity VL - 28 IS - 8 PB - Wiley PY - 2020 SN - 1930-7381 ER - TY - JOUR AB - Objective: This study aimed to determine the relationship between different forms of, and potential path-ways between, maternal diabetes and childhood obesity at different ages.Methods: Prospective cohort data from The Environmental Determinants of Diabetes in the Young (TEDDY) study, which was composed of 5,324 children examined from 0.25 to 6 years of age, were analyzed. Cross-sectional and longitudinal analyses taking into account potential confounders and effect modifiers such as maternal prepregnancy BMI and birth weight z scores were performed.Results: Offspring of mothers with gestational diabetes mellitus (GDM) or type 1 diabetes mellitus (TIDM) showed a higher BMI standard deviation score and increased risk for overweight and obesity at 5.5 years of age than offspring of mothers without diabetes. While these associations could be substantially explained by maternal pre-pregnancy BMI in offspring of mothers with GDM, significant associations disappeared after adjustment for birth weight z scores in offspring of T1DM mothers. Furthermore, overweight risk became stronger with increasing age in offspring of mothers with diabetes compared with offspring of mothers without diabetes.Conclusions: Maternal diabetes is associated with increased risk of offspring overweight, and the association appears to get stronger as children grow older. Indeed, intrauterine exposure to maternal T1DM may predispose children to later obesity through increased birth weight, while maternal BMI is more important in children exposed to GDM. AU - Pitchika, A. AU - Vehik, K.* AU - Hummel, S. AU - Norris, J.M.* AU - Uusitalo, U.M.* AU - Yang, J.* AU - Virtanen, S.M.* AU - Koletzko, S.* AU - Aronsson, C.A.* AU - Ziegler, A.-G. AU - Beyerlein, A. C1 - 54455 C2 - 45596 CY - 111 River St, Hoboken 07030-5774, Nj Usa SP - 1457-1466 TI - Associations of maternal diabetes during pregnancy with overweight in offspring: Results from the prospective TEDDY study. JO - Obesity VL - 26 IS - 9 PB - Wiley PY - 2018 SN - 1930-7381 ER - TY - JOUR AB - Objective: Weight loss maintenance is one of the biggest challenges in behavioral weight loss programs. The present study aimed to examine metabolic influences on the mesolimbic reward system in people with successful and unsuccessful long-term weight loss maintenance. Methods: Thirty-three women with obesity at least 6 months after the completion of a diet were recruited: seventeen women were able to maintain their weight loss, whereas sixteen showed weight regain. Using functional magnetic resonance imaging in combination with the assessment of appetite-regulating hormones, neural reward processing during hunger and satiety was investigated. An incentive delay task was employed to investigate the expectation and receipt of both food-related and monetary reward. Results: Only participants with successful weight loss maintenance showed a satiety-induced attenuation of brain activation during the receipt of a food-related reward. Furthermore, in successful weight loss maintenance, the attenuation of active ghrelin levels was related to brain activation in response to food-related reward anticipation during satiety. Conclusions: The findings suggest that an attenuated influence of satiety signaling on the neural processing of food-related reward contributes to unsuccessful weight loss maintenance. Thus, intact satiety signaling to the mesolimbic reward system may serve as a promising target for tackling weight cycling. AU - Simon, J.J.* AU - Becker, A.* AU - Sinno, M.H.* AU - Skunde, M.* AU - Bendszus, M.* AU - Preissl, H. AU - Enck, P.* AU - Herzog, W.* AU - Friederich, H.* C1 - 53814 C2 - 45040 CY - 233 Spring St, New York, Ny 10013 Usa SP - 895-902 TI - Neural food reward processing in successful and unsuccessful weight maintenance. JO - Obesity VL - 26 IS - 5 PB - Springer PY - 2018 SN - 1930-7381 ER - TY - JOUR AB - Objective: The associations of energy, protein, carbohydrate, and fat intake with weight status up to the age of 5.5 years were prospectively assessed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Methods: Food record data (over 3 days) and BMI measurements between 0.25 and 5.5 years were available from 5,563 children with an increased genetic risk for type 1 diabetes followed from shortly after birth. Odds ratios (ORs) were calculated for overweight and obesity by previous intake of energy, protein, carbohydrate, and fat with adjustment for potential confounders. Results: Having overweight or obesity at the age of 5.5 years was positively associated with mean energy intake in previous age intervals (e.g., adjusted OR [95% CI] for overweight: 1.06 [1.04-1.09] per 100 kcal intake at the age of 4.5-5.0 years) and with protein intake after the age of 3.5 and 4.5 years, respectively (e.g., adjusted OR for overweight: 1.06 [1.03-1.09] per 1% of energy intake at the age of 4.5-5.0 years). The respective associations with carbohydrate and fat intake were less consistent. Conclusions: These findings indicate that energy and protein intake are positively associated with increased risk for overweight in childhood but yield no evidence for potential programming effects of protein intake in infancy. AU - TEDDY Study Group (Beyerlein, A. AU - Winkler, C. AU - Ziegler, A.-G. AU - Hummel, S.) AU - Uusitalo, U.M.* AU - Virtanen, S.M.* AU - Vehik, K.* AU - Yang, J.* AU - Kersting, M.* AU - Koletzko, S.* AU - Schatz, D.* AU - Aronsson, C.A.* AU - Elding Larsson, H.* AU - Krischer, J.P.* AU - Norris, J.M.* C1 - 51479 C2 - 43148 CY - Hoboken SP - 1435-1441 TI - Intake of energy and protein is associated with overweight risk at age 5.5 years: Results from the prospective TEDDY study. JO - Obesity VL - 25 IS - 8 PB - Wiley PY - 2017 SN - 1930-7381 ER - TY - JOUR AB - ObjectiveGenome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with estimates of body fat distribution. Using predefined risk allele scores, the correlation of these scores with precisely quantified body fat distribution assessed by magnetic resonance (MR) imaging techniques and with metabolic traits was investigated. MethodsData from 4,944 MR scans from 915 subjects of European ancestry were analyzed. Body fat distribution was determined by MR imaging and liver fat content by H-1-MR spectroscopy. All subjects underwent a five-point 75-g oral glucose tolerance test. A total of 65 SNPs with reported genome-wide significant associations regarding estimates of body fat distribution were genotyped. Four genetic risk scores were created by summation of risk alleles. ResultsA higher allelic load of waist-to-hip ratio SNPs was associated with lower insulin sensitivity, higher postchallenge glucose levels, and more visceral and less subcutaneous fat mass. ConclusionsGWAS-derived polymorphisms estimating body fat distribution are associated with distinct patterns of body fat distribution exactly measured by MR. Only the risk score associated with the waist-to-hip ratio in GWAS showed an unhealthy pattern of metabolism and body fat distribution. This score might be useful for predicting diseases associated with genetically determined, unhealthy obesity. AU - Fehlert, E. AU - Wagner, R. AU - Ketterer, C. AU - Böhm, A. AU - Machann, J. AU - Fritsche, L. AU - Machicao, F. AU - Schick, F. AU - Staiger, H. AU - Stefan, N. AU - Häring, H.-U. AU - Fritsche, A. AU - Heni, M. C1 - 51511 C2 - 43501 CY - Hoboken SP - 1277-1283 TI - Genetic determination of body fat distribution and the attributive influence on metabolism. JO - Obesity VL - 25 IS - 7 PB - Wiley PY - 2017 SN - 1930-7381 ER - TY - JOUR AU - Kleinert, M. AU - Clemmensen, C. AU - Stemmer, K. AU - Müller, T.D. AU - DiMarchi, R.D.* AU - Tschöp, M.H. C1 - 52029 C2 - 43657 CY - Hoboken SP - 1647-1649 TI - Emerging poly-agonists for obesity and type 2 diabetes. JO - Obesity VL - 25 IS - 10 PB - Wiley PY - 2017 SN - 1930-7381 ER - TY - JOUR AB - OBJECTIVE: To investigate the association between long-term weight change and blood metabolites. METHODS: Change in BMI over 8.6 ± 3.79 years was assessed in 3,176 females from the TwinsUK cohort (age range: 18.3-79.6, baseline BMI: 25.11 ± 4.35) measured for 280 metabolites at follow-up. Statistically significant metabolites (adjusting for covariates) were included in a multivariable least absolute shrinkage and selection operator (LASSO) model. Findings were replicated in the Cooperative Health Research in the Region of Augsburg (KORA) study (n = 1,760; age range: 25-70, baseline BMI: 27.72 ± 4.53). The study examined whether the metabolites identified could prospectively predict weight change in KORA and in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) study (n = 471; age range: 55-74, baseline BMI: 27.24 ± 5.37). RESULTS: Thirty metabolites were significantly associated with change in BMI per year in TwinsUK using Bonferroni correction. Four were independently associated with weight change in the multivariable LASSO model and replicated in KORA: namely, urate (meta-analysis β [95% CI] = 0.05 [0.040 to 0.063]; P = 1.37 × 10(-19) ), gamma-glutamyl valine (β [95% CI] = 0.06 [0.046 to 0.070]; P = 1.23 × 10(-20) ), butyrylcarnitine (β [95% CI] = 0.04 [0.028 to 0.051]; P = 6.72 × 10(-12) ), and 3-phenylpropionate (β [95% CI] = -0.03 [-0.041 to -0.019]; P = 9.8 × 10(-8) ), all involved in oxidative stress. Higher levels of urate at baseline were associated with weight gain in KORA and PLCO. CONCLUSIONS: Metabolites linked to higher oxidative stress are associated with increased long-term weight gain. AU - Menni, C.* AU - Migaud, M.* AU - Kastenmüller, G. AU - Pallister, T.* AU - Zierer, J. AU - Peters, A. AU - Mohney, R.P.* AU - Spector, T.D.* AU - Bagnardi, V.* AU - Gieger, C. AU - Moore, S.C.* AU - Valdes, A.M.* C1 - 51647 C2 - 43407 SP - 1618-1624 TI - Metabolomic profiling of long-term weight change: Role of oxidative stress and urate levels in weight gain. JO - Obesity VL - 25 IS - 9 PY - 2017 SN - 1930-7381 ER - TY - JOUR AB - OBJECTIVE: To study the association between socioeconomic status (SES) and annual relative change in anthropometric markers in the general German adult population. METHODS: Longitudinal data of 56,556 participants aged 18-83 years from seven population-based German cohort studies (CARLA, SHIP, KORA, DEGS, EPIC-Heidelberg, EPIC-Potsdam, PopGen) were analyzed by meta-analysis using a random-effects model. The indicators of SES were education and household income. RESULTS: On average, all participants gained weight and increased their waist circumference over the study's follow-up period. Men and women in the low education group had a 0.1 percentage points greater annual increase in weight (95% CI men: 0.06-0.20; and women: 0.06-0.12) and waist circumference (95% CI men: 0.01-0.45; and women: 0.05-0.22) than participants in the high education group. Women with low income had a 0.1 percentage points higher annual increase in weight (95% CI 0.00-0.15) and waist circumference (95% CI 0.00-0.14) than women with high income. No association was found for men between income and obesity markers. CONCLUSIONS: Participants with lower SES (education and for women also income) gained more weight and waist circumference than those with higher SES. These results underline the necessity to evaluate the risk of weight gain based on SES to develop more effective preventive measures. AU - Herzog, B.* AU - Lacruz, M.E.* AU - Haerting, J.* AU - Hartwig, S.* AU - Tiller, D.* AU - Medenwald, D.* AU - Vogt, S. AU - Thorand, B. AU - Holle, R. AU - Bachlechner, U.* AU - Boeing, H.* AU - Merz, B.* AU - Nöthlings, U.* AU - Schlesinger, S.* AU - Schipf, S.* AU - Ittermann, T.* AU - Aumann, N.* AU - Schienkiewitz, A.* AU - Haftenberger, M.* AU - Greiser, K.H.* AU - Neamat-Allah, J.* AU - Katzke, V.A.* AU - Kluttig, A.* C1 - 47806 C2 - 39501 CY - Hoboken SP - 710-718 TI - Socioeconomic status and anthropometric changes - a meta-analytic approach from seven German cohorts. JO - Obesity VL - 24 IS - 3 PB - Wiley-blackwell PY - 2016 SN - 1930-7381 ER - TY - JOUR AB - OBJECTIVE: Whether specific combinations of risk factors in very early life might allow identification of high-risk target groups for overweight prevention programs was examined. DESIGN AND METHODS: Data of n = 8981 children from the German KiGGS study were analyzed. Using a classification tree approach, predictive risk factor combinations were assessed for overweight in 3-6, 7-10, and 11-17-year-old children. RESULTS: In preschool children, the subgroup with the highest overweight risk were migrant children with at least one obese parent, with a prevalence of 36.6 (95% confidence interval or CI: 22.9, 50.4)%, compared to an overall prevalence of 10.0 (8.9, 11.2)%. The prevalence of overweight increased from 18.3 (16.8, 19.8)% to 57.9 (46.6, 69.3)% in 7-10-year-old children, if at least one parent was obese and the child had been born large-for-gestational-age. In 11-17-year-olds, the overweight risk increased from 20.1 (18.9, 21.3)% to 63.0 (46.4, 79.7)% in the highest risk group. However, high prevalence ratios were found only in small subgroups, containing <10% of all overweight cases in the respective age group. CONCLUSIONS: Our results indicate only a limited potential for early targeted preventions against overweight in children and adolescents. AU - Beyerlein, A. AU - Kusian, D. AU - Ziegler, A.-G. AU - Schaffrath-Rosario, A.* AU - von Kries, R.* C1 - 28091 C2 - 32925 CY - Hoboken SP - 512–517 TI - Classification tree analyses reveal limited potential for early targeted prevention against childhood overweight. JO - Obesity VL - 22 IS - 1 PB - Nature Publishing PY - 2014 SN - 1930-7381 ER - TY - JOUR AB - Objective: The cannabinoid-receptor system is involved in the regulation of food intake. Here, we test whether single nucleotide polymorphisms (SNPs) in CNR2, encoding the cannabinoid-receptor 2, are associated with weight in a cross-sectional cohort. Furthermore, we wanted to investigate if the identified hits influence weight loss during lifestyle intervention; and study a potential involvement of cerebral insulin action. Methods: 2006 subjects at increased risk for type 2 diabetes mellitus were genotyped for 5 tagging SNPs in the CNR2 locus. All subjects underwent a 75-g OGTT. 345 subjects participated in a lifestyle intervention (TUebingen Lifestyle Intervention Programme). Cerebrocortical insulin sensitivity was measured by magnetoencephalography after intranasal insulin application in 43 subjects. Results: In the cross-sectional cohort, the minor allele of rs3123554 was associated with lower BMI (P-add = 0.01, P-rec = 0.004), and this was attributable to its effect in women only. Interestingly, during lifestyle intervention, carriers of the same allele lost less body weight (P-add = 0.03, P-rec = 0.008). Moreover, carriers of this minor allele showed lower cerebral insulin sensitivity (P-rec = 0.0402). Conclusions: The minor allele of rs3123554 is associated cross-sectionally with lower body weight, whereas during intervention the same allele led to less reduction of body weight. Reduced cerebral insulin sensitivity in carriers of this allele might contribute to these disadvantageous effects during lifestyle intervention. AU - Ketterer, C. AU - Heni, M.* AU - Stingl, K.T.* AU - Tschritter, O.* AU - Linder, K. AU - Wagner, R.* AU - Machicao, F. AU - Häring, H.-U. AU - Preissl, H. AU - Staiger, H. AU - Fritsche, A. C1 - 31086 C2 - 34238 CY - Hoboken SP - 925-931 TI - Polymorphism rs3123554 in CNR2 reveals gender-specific effects on body weight and affects loss of body weight and cerebral insulin action. JO - Obesity VL - 22 IS - 3 PB - Wiley-Blackwell PY - 2014 SN - 1930-7381 ER - TY - JOUR AB - Objective: While in adults not total body- or visceral fat mass, but liver fat content was found to independently determine insulin resistance, it is unclear whether these relationships are already present in obese adolescents. Design and Methods: 39 overweight/ obese adolescents were matched for sex and BMI with 39 adults. To compare the age- and sex-specific BMI values of adolescents and adults, the percentile value of each adolescent was projected to the age of 18. Body fat depots were quantified by whole-body magnetic resonance (MR) imaging. Liver fat content was measured with (1) H-MR spectroscopy. Insulin resistance was estimated from the homeostasis model assessment of insulin resistance (HOMA-IR). Results: Compared to overweight and obese adults, adolescents had higher HOMA-IR (p<0.001) and lower lean body mass (p=0.002). Furthermore, they had higher total body- (p=0.02), but lower visceral- (p<0.001) fat mass, while liver fat content was not significantly different between the groups (p=0.16). In both groups liver fat content (both p≤0.007), but not total body- or visceral fat mass (all p≥0.64) was an independent predictor of insulin resistance. Conclusions: Having lower visceral fat mass, overweight and obese adolescents are more insulin resistant than sex- and BMI-matched adults. Liver fat content, but not total body- or visceral fat mass, is an independent determinant of insulin resistance in adolescents. AU - Linder, K. AU - Springer, F.* AU - Machann, J. AU - Schick, F. AU - Fritsche, A. AU - Häring, H.-U. AU - Blumenstock, G.* AU - Ranke, M.B.* AU - Stefan, N. AU - Binder, G.* AU - Ehehalt, S.* C1 - 30728 C2 - 33799 CY - Hoboken SP - 733-748 TI - Relationships of body composition and liver fat content with insulin resistance in obesity-matched adolescents and adults. JO - Obesity VL - 13 IS - 5 PB - Wiley-Blackwell PY - 2014 SN - 1930-7381 ER - TY - JOUR AB - Objective Lifestyle interventions including reduction of caloric intake are still the most pursued option to treat obesity. However, their outcome in terms of weight loss strongly differs between participants. In our study, we hypothesized that initial differences in brain activation in a food specific memory task are associated with weight change during a lifestyle intervention. Design and Methods Magnetic brain activity was recorded during a one-back visual memory task with food and nonfood pictures in 33 overweight and obese subjects before they underwent a lifestyle intervention. The intervention lasted 6 months and aimed for a reduction in daily caloric intake by 400 kcal. Body mass index (BMI) was determined before and after the intervention. Results Differences between outer tertiles representing people who increased their BMI by 1.4% +/- 1.1% (non-responders) and who reduced their BMI by -6.9% +/- 2.6% (responders) are reported. Neuronal activity was related to BMI change in sensor and source space. Non-responders showed higher activation in right inferior frontal and left occipital visual areas, whereas responders showed increased activation in right temporal areas including hippocampus and fusiform gyrus. Conclusions Differences in the cerebral response during a food specific memory task indicate an altered cognitive control over food intake. These differences might determine the ability to eat less and successfully lose weight. AU - Hege, M.A.* AU - Stingl, K.T.* AU - Ketterer, C.* AU - Häring, H.-U. AU - Heni, M.* AU - Fritsche, A. AU - Preissl, H. C1 - 29330 C2 - 33719 SP - 2488-2494 TI - Working memory-related brain activity is associated with outcome of lifestyle intervention. JO - Obesity VL - 21 IS - 12 PB - Wiley-Blackwell PY - 2013 SN - 1930-7381 ER - TY - JOUR AB - Objective: To evaluate if percentile-specific effects of genetic, environmental and lifestyle obesity risk factors on body mass index (BMI) might reflect gene-environment interactions with respect to the development of overweight. Design and Methods: Retrospective study with data of 2,346 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), using quantile regression with body fat mass index (FMI) for children at the age of 9 years as outcome variable. We assessed interactions of an “obesity-risk-allele-score” with environmental and nutritional factors. Results: There was no evidence of interactions between the obesity-risk-allele score and the environmental variables except for maternal overweight. However, we found a significant interaction with respect to intake of mono- and polyunsaturated fatty acids at the age of 7. In children with low intake, genetic risk was associated with increasing effect sizes by FMI percentile. Conclusions: Our results suggest an interaction between a low dietary content of unsaturated fatty acids and genetic risk factors for overweight on FMI. This effect is likely to be stronger in children with higher FMI.   AU - Riedel, C.* AU - von Kries, R.* AU - Fenske, N.* AU - Strauch, K. AU - Ness, A.R.* AU - Beyerlein, A. C1 - 23056 C2 - 30988 SP - 1238-1242 TI - Interactions of genetic and environmental risk factors with respect to body fat mass in children: Results from the ALSPAC study. JO - Obesity VL - 21 IS - 6 PB - Wiley-Blackwell PY - 2013 SN - 1930-7381 ER - TY - JOUR AB - OBJECTIVE: Overweight and obesity are associated with a dyslipidaemia which can be improved by weight loss. Whether genetic predisposition to an adverse lipid profile modifies such beneficial effects of weight loss on lipid levels in overweight and obese individuals was examined. DESIGN AND METHODS: White European participants (n = 374) who completed a 12-month weight loss trial were genotyped for 36 lipid-associated single nucleotide polymorphisms (SNPs), previously identified in genome-wide association studies (GWAS). Genetic predisposition scores (GPSs) were calculated for four lipid traits by summing the number of risk alleles (RA) for each participant. The associations of each GPS with four lipid traits were assessed at baseline, and with lipid changes in response to weight change after 12 months. RESULTS: At baseline, the trait-specific GPSs were associated with 0.11 ± 0.04 mM higher total cholesterol/RA (P = 0.004), 0.05 ± 0.02 mM higher low density lipoprotein cholesterol/RA (P = 0.005), 0.03 ± 0.007 mM lower high density lipoprotein cholesterol/RA (P = 0.00002) and 0.04 ± 0.01 mM higher triglyceride/RA (P = 0.00002). After the intervention, weight loss was associated with improvements in all lipids (P < 0.01). GPS attenuated the weight loss-associated reduction in TC so those with a higher GPS had less improvement (interaction = 0.01 ± 0.005 mM/GPS/kg weight loss, P = 0.003). A similar pattern was observed for LDLC (interaction = 0.004 ± 0.002 mM/GPS/kg weight loss, P = 0.07). There was no evidence of a GPS-modifying effect for change in HDLC or TG. CONCLUSION: Genetic predisposition is an important determinant of lipid levels and appears to limit the improvement in TC and to some extent LDLC levels, but not in other plasma lipids, in response to weight loss. AU - Walker, C.G.* AU - Holzapfel, C. AU - Loos, R.J.* AU - Mander, A.P.* AU - Klopp, N.* AU - Illig, T.* AU - Caterson, I.D.* AU - Hauner, H.* AU - Jebb, S.A.* C1 - 28936 C2 - 33586 SP - 2589-2595 TI - Genetic predisposition to an adverse lipid profile limits the improvement in total cholesterol in response to weight loss. JO - Obesity VL - 21 IS - 12 PB - Wiley-Blackwell PY - 2013 SN - 1930-7381 ER - TY - JOUR AB - Genome-wide association analyses (GWAS) contributed to the detection of a number of single-nucleotide polymorphisms (SNPs) associated with obesity. However, little is known about the impact of the obesity-risk alleles on weight loss-related phenotypes after lifestyle interventions. A recent meta-analysis of GWAS reported five genomic loci near or in the genes FTO, MC4R, TMEM18, SDCCAG8, TNKS/MSRA that were associated with obesity in children and adolescents. Here, we analyzed the effect of the 10 SNPs representative of the five loci on measures of weight loss and cardiometabolic risk after a 1-year lifestyle intervention in 401 children and adolescents (mean age 10.74 years; 55.4% female; mean BMI 27.42 kg/m(2), mean BMI-standard deviation score (SDS) 2.37). For confirmation of one locus genotyping of three intronic SNPs in SDCCAG8 was performed in 626 obese adults who completed the 10-week hypoenergetic diet program. Intronic variants of SDCCAG8, which are associated with early onset obesity, are associated with reduced weight loss after a 1-year lifestyle intervention in overweight children and adolescents even after adjusting for age, sex, baseline measurement, or multiple testing (all P < 10(-6)). However, our results could not be confirmed in 626 obese adults undertaking a hypoenergetic diet intervention. AU - Scherag, A.* AU - Kleber, M.* AU - Boes, T.* AU - Kolbe, A.L.* AU - Ruth, A.* AU - Grallert, H. AU - Illig, T. AU - Heid, I.M. AU - GIANT Consortium (Gieger, C. AU - Thiering, E. AU - Meitinger, T. AU - Heinrich, J. AU - Peters, A. AU - Wichmann, H.-E. AU - Illig, T. AU - Grallert, H.) AU - Toschke, A.M.* AU - Grau, K.* AU - NUGENOB Consortium (*) AU - Sørensen, T.I.* AU - Hebebrand, J.* AU - Hinney, A.* AU - Reinehr, T.* C1 - 7215 C2 - 29552 SP - 466-470 TI - SDCCAG8 obesity alleles and reduced weight loss after a lifestyle intervention in overweight children and adolescents. JO - Obesity VL - 20 IS - 2 PB - Nature Publishing Group PY - 2012 SN - 1930-7381 ER - TY - JOUR AB - We investigated associations of markers of inflammation such as albumin, fibrinogen, C-reactive protein (CRP), and white blood cell count (WBCC) with future weight gain and weight loss in middle-aged adults in order to further elucidate the relationship between subclinical inflammation and weight change. Data were derived from the third population-based MONICA (Monitoring of Trends and Determinants in Cardiovascular Diseases) Augsburg survey (S3) conducted as part of the multinational World Health Organization MONICA project in 1994-1995 and a follow-up examination, to which all eligible subjects from S3 were invited in 2004-2005 (F3). In total, 2,792 persons (1,391 men, 1,401 women) aged 25-74 years at baseline were analyzed. Subjects with elevated concentrations of inflammatory markers were more prone to gain weight during follow-up. The odds ratios (OR) for a large mean annual weight gain (i.e., on average 1.02 kg/year) was 1.73 (95% confidence interval (CI) 1.27, 2.35) in fully adjusted analyses for subjects in the highest compared to the lowest quartile of fibrinogen. The respective ORs were 1.45 (95% CI, 1.08, 1.94) and 1.37 (95% CI, 1.03, 1.82) for CRP and WBCC. Stratified analyses revealed that associations were strongest among subjects who quitted smoking during the follow-up period (new quitters). Associations of inflammatory markers with large mean annual weight loss were weaker and became nonsignificant after multivariable adjustment. In conclusion, elevated levels of inflammatory markers are independently associated with weight gain in middle-aged adults, particularly among new quitters. This suggests that inflammation plays a key role in the process of weight gain, especially after smoking cessation. AU - Holz, T. AU - Thorand, B. AU - Döring, A. AU - Schneider, A.E. AU - Meisinger, C. AU - Koenig, W.* C1 - 5310 C2 - 27922 SP - 2347-2353 TI - Markers of inflammation and weight change in middle-aged adults: Results from the prospective MONICA/KORA S3/F3 study. JO - Obesity VL - 18 IS - 12 PB - Nature Publ. Group PY - 2010 SN - 1930-7381 ER - TY - JOUR AU - Sausenthaler, S. AU - Rzehak, P. AU - Wichmann, H.-E. AU - Heinrich, J. C1 - 2244 C2 - 26142 SP - 937-938 TI - Lack of relation between bitter taste receptor TAS2R38 and BMI in adults. JO - Obesity VL - 17 IS - 5 PB - Nature Publ. Group PY - 2009 SN - 1930-7381 ER - TY - JOUR AB - A previous epidemiological study showed an association of the insulin-induced gene 2 (INSIG2) gene with BMI. Additionally, experimental investigations in animals and cell culture provided evidence that this gene might be involved in lipoprotein and free fatty acid (FFA) metabolism. Therefore, the aim of this study was to examine the association between the rs7566605 variant near the INSIG2 gene and BMI and to extend it to other quantitative measures of obesity, as well as parameters of lipoprotein and FFA metabolism. METHODS AND PROCEDURES: We genotyped rs7566605 in a group of severely obese white patients (n = 1,026) with an average BMI of 46.0 kg/m(2) and a control group (n = 818) from Utah, as well as in the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study from Austria, which is based on a healthy working population (n = 1,696). RESULTS: We observed no difference in the genotype frequency of rs7566605 of INSIG2 between obese subjects and population-based controls from Utah. Furthermore, we did not find evidence of an association with measures of body composition (BMI, waist, waist-to-hip ratio, percentage body fat, amount of visceral and subcutaneous abdominal adipose fat) or lipoprotein metabolism (total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and FFAs) in the Utah study population or in the independent SAPHIR study. DISCUSSION: Our results do not support an association of the INSIG2 gene with the regulation of body weight or parameters related to lipoprotein metabolism. AU - Boes, E.* AU - Kollerits, B.* AU - Heid, I.M. AU - Hunt, S.C.* AU - Pichler, M.* AU - Paulweber, B.* AU - Coassin, S.* AU - Adams, T.D.* AU - Hopkins, P.N.* AU - Lingenhel, A.* AU - Wagner, S.A.* AU - Kronenberg, F.* C1 - 2576 C2 - 25293 SP - 827-833 TI - INSIG2 polymorphism is neither associated with BMI nor with phenotypes of lipoprotein metabolism. JO - Obesity VL - 16 IS - 4 PB - Nature Publ. Group PY - 2008 SN - 1930-7381 ER - TY - JOUR AB - Previous studies have described genetic associations of the insulin gene variable number tandem repeat (INS VNTR) variant with childhood obesity and associated phenotypes. We aimed to assess the contribution of INS VNTR genotypes to childhood obesity and variance of insulin resistance, insulin secretion, and birth weight using family-based design. Participants were either French or German whites. We used transmission disequilibrium tests (TDTs) for assessing binary traits and quantitative pedigree disequilibrium tests for assessing continuous traits. In contrast to previous findings, we did not observe any familial association with childhood obesity (T = 50%, P = 0.77) in the 1,023 families tested. In French obese children, INS VNTR did not associate with fasting insulin levels (P = 0.23) and class I allele showed only borderline association with increased insulin secretion index at 30 min (P = 0.03). INS VNTR did not associate with birth weight in obese children (P = 0.98) and TDT analyses in 350 French families with history of low birth weight (LBW) showed no association with this condition (P = 0.92). In summary, our study, the largest performed so far, does not support the previously reported associations between INS VNTR and childhood obesity, insulin resistance, or birth weight, and does not suggest any major role for this variant in modulating these traits. AU - Bouatia-Naji, N.* AU - De, Graeve, F.* AU - Brönner, G.* AU - Lecoeur, C.* AU - Vatin, V.* AU - Durand, E.* AU - Lichtner, P. AU - Nguyen, T.T.* AU - Heude, B.* AU - Weill, J.* AU - Lévy-Marchal, C.* AU - Hebebrand, J.* AU - Froguel, P.* AU - Meyre, D.* C1 - 1826 C2 - 25617 SP - 1471-1475 TI - INS VNTR is not associated with childhood obesity in 1,023 families: A family-based study. JO - Obesity VL - 16 IS - 6 PB - Nature Publ. Group PY - 2008 SN - 1930-7381 ER - TY - JOUR AB - Epidemiological studies showing an association between the melanocortin-4-receptor (MC4R) 103I variant (rs2229616) and decreased BMI are complemented by functional studies; these suggest a mechanism for appetite regulation and a linkage signal for physical activity and dietary intake for the region encompassing the MC4R. This study aims to provide epidemiological evidence for showing the association of this polymorphism with features of the metabolic syndrome and with parameters related to energy expenditure and dietary habits as potential mediators. METHODS AND PROCEDURES: We analyzed this polymorphism in 7,888 adults of a population-based cross-sectional study applying regression-based statistical models. RESULTS: Carriers of the MC4R 103I (3.7%) exhibited a significantly decreased waist circumference (-1.46 cm, P = 0.020), decreased glycosylated hemoglobin (HbA(1c)) (-0.09%, P = 0.040), and increased HDL-cholesterol (HDL-C) (+1.76 mg/dl, P = 0.056), but no change in blood pressure. The odds of having three or more components of the metabolic syndrome were substantially reduced among carriers of MC4R 103I (odds ratio (OR) = 0.46, P = 0.003). Controlling for BMI reduced the HbA(1c) and HDL-C association. Mediator analyses revealed a borderline association of MC4R 103I with carbohydrate intake (OR = 1.26, P = 0.059) possibly mediating association with leanness. DISCUSSION: Our representative study of well-phenotyped Europeans is the first to describe the association of the MC4R V103I with the metabolic syndrome and with a nutrient-related phenotype. Our data support the idea that this polymorphism plays a role in appetite regulation that not only affects BMI, but also other features of the metabolic syndrome. It further establishes that the association of the MC4R V103I with obesity and related phenotypes is genuine. AU - Heid, I.M. AU - Vollmert, C. AU - Kronenberg, F.* AU - Huth, C. AU - Ankerst, D.P.* AU - Luchner, A.* AU - Hinney, A.* AU - Brönner, G.* AU - Wichmann, H.-E. AU - Illig, T. AU - Döring, A. AU - Hebebrand, J.* C1 - 4629 C2 - 25271 SP - 369-376 TI - Association of the MC4R V103I polymorphism with the metabolic syndrome: The KORA Study. JO - Obesity VL - 16 IS - 9 PB - Nature Publ. Group PY - 2008 SN - 1930-7381 ER - TY - JOUR AU - Meisinger, C. AU - Heier, M. AU - Löwel, H. C1 - 1563 C2 - 22464 SP - 1473-1480 TI - The relationship between body weight and health care among German woman. JO - Obesity VL - 12 PY - 2004 SN - 1930-7381 ER -