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Dong, Q. ; Sidra, S.* ; Gieger, C. ; Wang-Sattler, R. ; Rathmann, W.* ; Prehn, C. ; Adamski, J. ; Koenig, W.* ; Peters, A. ; Grallert, H. ; Sharma, S.

Metabolic signatures elucidate the effect of body mass index on type 2 diabetes.

Metabolites 13:227 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Obesity plays an important role in the development of insulin resistance and diabetes, but the molecular mechanism that links obesity and diabetes is still not completely understood. Here, we used 146 targeted metabolomic profiles from the German KORA FF4 cohort consisting of 1715 participants and associated them with obesity and type 2 diabetes. In the basic model, 83 and 51 metabolites were significantly associated with body mass index (BMI) and T2D, respectively. Those metabolites are branched-chain amino acids, acylcarnitines, lysophospholipids, or phosphatidylcholines. In the full model, 42 and 3 metabolites were significantly associated with BMI and T2D, respectively, and replicate findings in the previous studies. Sobel mediation testing suggests that the effect of BMI on T2D might be mediated via lipids such as sphingomyelin (SM) C16:1, SM C18:1 and diacylphosphatidylcholine (PC aa) C38:3. Moreover, mendelian randomization suggests a causal relationship that BMI causes the change of SM C16:1 and PC aa C38:3, and the change of SM C16:1, SM C18:1, and PC aa C38:3 contribute to T2D incident. Biological pathway analysis in combination with genetics and mice experiments indicate that downregulation of sphingolipid or upregulation of phosphatidylcholine metabolism is a causal factor in early-stage T2D pathophysiology. Our findings indicate that metabolites like SM C16:1, SM C18:1, and PC aa C38:3 mediate the effect of BMI on T2D and elucidate their role in obesity related T2D pathologies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Mediation ; Mendelian Randomization ; Metabolomics ; Obesity ; Type 2 Diabetes ; Type 2 Diabetes Pathology; Novo Sphingolipid Biosynthesis; Polyunsaturated Fatty-acids; Chain Amino-acids; Insulin-resistance; Wide Association; Obesity; Expression; Inflammation; Sensitivity; Desaturase
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 2218-1989
e-ISSN 2218-1989
Zeitschrift Metabolites
Quellenangaben Band: 13, Heft: 2, Seiten: , Artikelnummer: 227 Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Translational Genomics (ITG)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Experimental Genetics (IEG)
POF Topic(s) 30202 - Environmental Health
30205 - Bioengineering and Digital Health
30505 - New Technologies for Biomedical Discoveries
30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-504091-002
G-504090-001
G-504091-004
G-506700-001
A-630710-001
G-500600-001
G-504000-010
G-504091-003
Förderungen China Scholarship Council (CSC)
DOI 10.3390/metabo13020227
WOS ID 000940617000001
Scopus ID 85148899521
PubMed ID 36837846
Erfassungsdatum 2023-03-01
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