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Dieckmann, S.* ; Strohmeyer, A.* ; Willershäuser, M.* ; Maurer, S.F.* ; Wurst, W. ; Marschall, S. ; Hrabě de Angelis, M. ; Kühn, R. ; Worthmann, A.* ; Fuh, M.M.* ; Heeren, J.* ; Pauling, J.K.* ; Klingenspor, M.*

Susceptibility to diet-induced obesity at thermoneutral conditions is independent of UCP1.

Am. J. Physiol. Endocrinol. Metab. 322, E85-E100 (2022)
Verlagsversion Postprint DOI PMC
Open Access Gold
Objective Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity. However, studies investigating the role of UCP1 to protect against diet-induced obesity are controversial and rely on the phenotyping of a single constitutive UCP1-knockout model. To address this issue, we generated a novel UCP1-knockout model by Cre-mediated deletion of Exon 2 in the UCP1 gene. We studied the effect of constitutive UCP1 knockout on metabolism and the development of diet-induced obesity. Methods UCP1 knockout and wildtype mice were housed at 30°C and fed a control diet for 4-weeks followed by 8-weeks of high-fat diet. Body weight and food intake were monitored continuously over the course of the study and indirect calorimetry was used to determine energy expenditure during both feeding periods. Results Based on Western blot analysis, thermal imaging and noradrenaline test, we confirmed the lack of functional UCP1 in knockout mice. However, body weight gain, food intake and energy expenditure were not affected by deletion of UCP1 gene function during both feeding periods. Conclusion We introduce a novel UCP1-KO mouse enabling the generation of conditional UCP1-knockout mice to scrutinize the contribution of UCP1 to energy metabolism in different cell types or life stages. Our results demonstrate that UCP1 does not protect against diet-induced obesity at thermoneutrality.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Uncoupling Protein 1 ; Adipose Tissue ; Diet Induced Obesity ; Thermogenesis; Brown Adipose-tissue; Induced Thermogenesis; Adaptive Thermogenesis; Uncoupling Protein; Energy-expenditure; Gut Microbiota; Wild-type; Cold; Mice; Fat
Sprache englisch
Veröffentlichungsjahr 2022
Prepublished im Jahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 0193-1849
e-ISSN 1522-1555
Zeitschrift American Journal of Physiology - Endocrinology and Metabolism
Quellenangaben Band: 322, Heft: 2, Seiten: E85-E100 Artikelnummer: , Supplement: ,
Verlag American Physiological Society
Verlagsort 6120 Executive Blvd, Suite 600, Rockville, Md, United States
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
POF Topic(s) 30204 - Cell Programming and Repair
30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500500-001
G-500600-001
Förderungen Bavarian State Ministry of Education, Science and the Arts | Elitenetzwerk Bayern (Elite Network of Bavaria)
European Commission (EC)
Else Kröner-Fresenius-Stiftung (EKFS)
Agence nationale de la recherche (ANR)
Deutsche Forschungsgemeinschaft (DFG)
DOI 10.1152/ajpendo.00278.2021
WOS ID WOS:000753820300001
Scopus ID 85123879045
PubMed ID 34927460
Erfassungsdatum 2022-01-10
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