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Leiss, V.* ; Schönsiegel, A.* ; Gnad, T.* ; Kerner, J.* ; Kaur, J.* ; Sartorius, T. ; Machann, J. ; Schick, F.* ; Birnbaumer, L.* ; Häring, H.U.* ; Pfeifer, A.* ; Nürnberg, B.*

Lack of Gαi2 proteins in adipocytes attenuates diet-induced obesity.

Mol. Metab. 40:101029 (2020)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
Objectives: Typically, obesity results from an inappropriate balance between energy uptake from nutrient consumption and burning of calories, which leads to a pathological increase in fat mass. Obesity is a major cause of insulin resistance and diabetes. Inhibitory G proteins (G alpha(i)) form a subfamily that is involved in the regulation of adipose tissue function. Among the three Gai members, i.e. G alpha(i1), G alpha(i2), G alpha(i3), the G alpha(i2), protein is predominantly expressed in adipose tissue. However, the functions of the G alpha(i2) isoform in adipose tissue and its impact on the development of obesity are poorly understood.Methods: By using AdipoqCreER(T2) mice, we generated adipocyte-specific Gnai2-deficient mice to study G alpha(i2) function, specifically in white and brown adipocytes. These mice were fed either a control diet (CD) or a high fat diet (HFD). Mice were examined for obesity development, insulin resistance and glucose intolerance. We examined adipocyte morphology and the development of inflammation in the white adipose tissue. Finally, intracellular cAMP levels as an indicator of Gai signaling and glycerol release as an indicator of lipolysis rates were measured to verify the impact of G alpha(i2) on the signaling pathway in brown and white adipocytes.Results: An adipocyte-specific deficiency of G alpha(i2) significantly reduced diet-induced obesity, leading to decreased fat masses, smaller adipocytes and decreased inflammation in the white adipose tissue relative to littermate controls. Concurrently, oxygen consumption of brown adipocytes and in vivo measured energy expenditure were significantly enhanced. In addition, glucose tolerance and insulin sensitivity of HFD-fed adipocyte-specific Gnai2-deficient mice were improved compared to the respective controls. In the absence of G alpha(i2), adrenergic stimulation of intracellular adipocyte cAMP levels was increased, which correlated with increased lipolysis and energy expenditure.Conclusion: We conclude that adipocyte G alpha(i2) is a major regulator of adipocyte lipid content in diet-induced obesity by inhibiting adipocyte lipolysis in a cAMP-dependent manner resulting in increased energy expenditure.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Adipocytes ; Brown Adipose Tissue ; Gnai2 ; G Proteins ; High Fat Diet ; Insulin ; Obesity ; White Adipose Tissue; Adipose-tissue; Insulin; Alpha; Inflammation; Expression; Resistance; Lipolysis; G(i3); Il-6
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 40, Heft: , Seiten: , Artikelnummer: 101029 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Förderungen Intramural Research Program of the NIH
German Research Foundation (DFG)