Growth hormone controls lipolysis by regulation of FSP27 expression

in Journal of Endocrinology
Authors:
Rita Sharma Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Quyen Luong Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Vishva M Sharma Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Mitchell Harberson Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Brian Harper Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Andrew Colborn Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Darlene E Berryman Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Niels Jessen Research Laboratory for Biochemical Pathology, Aarhus University Hospital, Aarhus, Denmark
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Biomedicine, Aarhus University, Aarhus, Denmark

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Jens Otto Lunde Jørgensen Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Medical Research Laboratory, Aarhus University, Aarhus, Denmark

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John J Kopchick Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA
Edison Biotechnology Institute, Ohio University, Athens, Ohio, USA

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Vishwajeet Puri Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Kevin Y Lee Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA
The Diabetes Institute, Ohio University, Athens, Ohio, USA

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Correspondence should be addressed to V Puri or K Y Lee: puri@ohio.edu or leek2@ohio.edu

*(R Sharma, Q Luong and V M Sharma contributed equally to this work)

DOI:
https://doi.org/10.1530/JOE-18-0282
Volume/Issue:
Volume 239: Issue 3
Article Type:
Research Article
Page Range:
289–301
Online Publication Date:
Dec 2018
Copyright:
© 2018 Society for Endocrinology 2018
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Growth hormone (GH) has long been known to stimulate lipolysis and insulin resistance; however, the molecular mechanisms underlying these effects are unknown. In the present study, we demonstrate that GH acutely induces lipolysis in cultured adipocytes. This effect is secondary to the reduced expression of a negative regulator of lipolysis, fat-specific protein 27 (FSP27; aka Cidec) at both the mRNA and protein levels. These effects are mimicked in vivo as transgenic overexpression of GH leads to a reduction of FSP27 expression. Mechanistically, we show GH modulation of FSP27 expression is mediated through activation of both MEK/ERK- and STAT5-dependent intracellular signaling. These two molecular pathways interact to differentially manipulate peroxisome proliferator-activated receptor gamma activity (PPARγ) on the FSP27 promoter. Furthermore, overexpression of FSP27 is sufficient to fully suppress GH-induced lipolysis and insulin resistance in cultured adipocytes. Taken together, these data decipher a molecular mechanism by which GH acutely regulates lipolysis and insulin resistance in adipocytes.

Supplementary Materials

    • Supplemental Figure 1
    • Supplemental Figure 2
    • Supplemental Figure 3
    • Supplemental Figure 4
    • Supplemental Table 1. Primer Sequences
    • Supplemental Table 2. Antibodies

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2018 Society for Endocrinology 2018
Page(s):
13
Article Type:
Research Article
Received Date:
13 Sep 2018
Accepted Date:
24 Sep 2018
Print Publication Date:
01 Dec 2018
Online Publication Date:
Dec 2018
Keywords:
PPPAR-gamma; metabolism; acromegaly; adipose tissue; obesity; diabetes