Adipocyte subpopulations mediate lipolysis and obesity-induced insulin resistance

in Journal of Endocrinology
Authors:
Jun Huang Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA

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https://orcid.org/0009-0009-6178-8456
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Rita Sharma Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA

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Sohana Siyar Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA

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Vishva 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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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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https://orcid.org/0000-0002-1528-7417

Correspondence should be addressed to K Y Lee: leek2@ohio.edu
DOI:
https://doi.org/10.1530/JOE-23-0149
Volume/Issue:
Volume 260: Issue 3
Article Type:
Research Article
Article ID:
e230149
Online Publication Date:
22 Jan 2024
Copyright:
© the author(s) 2024
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Studies in humans and mice have determined that distinct subpopulations of adipocytes reside even within individual adipose tissue depots. Previously, our lab defined three white adipocyte subpopulations with stable and unique gene expression profiles, which were termed type 1, 2, and 3 adipocytes, respectively. Our previous studies demonstrated that type 2 adipocytes were highly responsive to the inflammatory cytokine, tumor necrosis factor alpha (TNFα). This study extends these findings to investigate the role of type 2 adipocytes in obesity. We found that treatment with TNFα increased lipolysis specifically in type 2 adipocytes, at least in part, through the reduction of fat-specific protein 27 (FSP27) expression. To assess the physiological role of lipolysis from this adipocyte subpopulation, a type2Ad-hFSP27tg mouse model was generated by overexpressing human FSP27 specifically in type 2 adipocytes. Glucose and insulin tolerance test analysis showed that male type2Ad-hFSP27tg mice on 60% high-fat diet exhibited improved glucose tolerance and insulin sensitivity, with no change in body weight compared to controls. These metabolic changes may, at least in part, be explained by the reduced lipolysis rate in the visceral fat of type2Ad-hFSP27tg mice. Although FSP27 overexpression in primary type 2 adipocytes was sufficient to acutely reduce TNFα-induced apoptosis in vitro, it failed to reduce macrophage infiltration in obesity in vivo. Taken together, these results strongly suggest that type 2 adipocytes contribute to the regulation of lipolysis and could serve as a potential therapeutic target for obesity-associated insulin resistance.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2024
Article ID:
e230149
Article Type:
Research Article
Received Date:
10 May 2023
Accepted Date:
04 Jan 2024
Print Publication Date:
01 Mar 2024
Online Publication Date:
22 Jan 2024
Keywords:
subpopulation; macrophage; obesity; adipose tissue; TNFα

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