Adipocyte Subpopulations Mediate Growth Hormone-induced Lipolysis and Glucose Tolerance in Male Mice

Author:

Huang Jun1ORCID,Siyar Sohana1,Sharma Rita1,Herrig Isabella1,Wise Lauren1,Aidt Spencer1,List Edward12,Kopchick John J12ORCID,Puri Vishwajeet12,Lee Kevin Y12ORCID

Affiliation:

1. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University , Athens, OH 45701 , USA

2. The Diabetes Institute, Ohio University , Athens, OH 45701 , USA

Abstract

Abstract In adipose tissue, growth hormone (GH) stimulates lipolysis, leading to an increase in plasma free fatty acid levels and a reduction in insulin sensitivity. In our previous studies, we have found that GH increases lipolysis by reducing peroxisome proliferator-activated receptor γ (PPARγ) transcription activity, leading to a reduction of tat-specific protein 27 (FSP27, also known as CIDEC) expression. In previous studies, our laboratory uncovered 3 developmentally distinct subpopulations of white adipocytes. In this manuscript, we show that one of the subpopulations, termed type 2 adipocytes, has increased GH-induced signaling and lipolysis compared to other adipocyte subtypes. To assess the physiological role of GH-mediated lipolysis mediated by this adipocyte subpopulation, we specifically expressed human FSP27 (hFSP27) transgene in type 2 adipocytes (type2Ad-hFSP27tg mice). Systemically, male type2Ad-hFSP27tg mice displayed reduced serum glycerol release and nonesterified fatty acids levels after acute GH treatment, and improvement in acute, but not chronic, GH-induced glucose intolerance. Furthermore, we demonstrate that type2Ad-hFSP27tg mice displayed improved hepatic insulin signaling. Taken together, these results indicate that this adipocyte subpopulation is a critical regulator of the GH-mediated lipolytic and metabolic response. Thus, further investigation of adipocyte subpopulations may provide novel treatment strategies to regulate GH-induced glucose intolerance in patients with growth and metabolic disorders.

Funder

Ohio University College of Osteopathic Medicine

American Diabetes Association Junior Faculty Development

Growth Innovation

EMD Serono

Pfizer

Publisher

The Endocrine Society

Subject

Endocrinology

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