Sommer, Judith and Ehnis, Hanna and Seitz, Tatjana and Schneider, Julia and Wild, Andreas B. and Moceri, Sandra and Buechler, Christa and Bozec, Aline and Weber, Georg F. and Merkel, Susanne and Beckervordersandforth, Ruth and Steinkasserer, Alexander and Schuele, Roland and Trebicka, Jonel and Hartmann, Arndt and Bosserhoff, Anja and von Hoersten, Stephan and Dietrich, Peter and Hellerbrand, Claus (2023) Four-and-a-Half LIM-Domain Protein 2 (FHL2) Induces Neuropeptide Y (NPY) in Macrophages in Visceral Adipose Tissue and Promotes Diet-Induced Obesity. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (19): 14943. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues. In this study, we aimed to gain new insights into the expression and functional role of FHL2 in VAT in diet-induced obesity. We found enhanced FHL2 expression in the VAT of mice with Western-type diet (WTD)-induced obesity and obese humans and identified macrophages as the cellular source of enhanced FHL2 expression in VAT. In mice with FHL2 deficiency (FHL2KO), WTD feeding resulted in reduced body weight gain paralleled by enhanced energy expenditure and uncoupling protein 1 (UCP1) expression, indicative of activated thermogenesis. In human VAT, FHL2 was inversely correlated with UCP1 expression. Furthermore, macrophage infiltration and the expression of the chemokine MCP-1, a known promotor of macrophage accumulation, was significantly reduced in WTD-fed FHL2KO mice compared with wild-type (wt) littermates. While FHL2 depletion did not affect the differentiation or lipid metabolism of adipocytes in vitro, FHL2 depletion in macrophages resulted in reduced expressions of MCP-1 and the neuropeptide Y (NPY). Furthermore, WTD-fed FHL2KO mice showed reduced NPY expression in VAT compared with wt littermates, and NPY expression was enhanced in VAT resident macrophages of obese individuals. Stimulation with recombinant NPY induced not only UCP1 expression and lipid accumulation but also MCP-1 expression in adipocytes. Collectively, these findings indicate that FHL2 is a positive regulator of NPY and MCP-1 expression in macrophages and herewith closely linked to the mechanism of obesity-associated lipid accumulation and inflammation in VAT. Thus, FHL2 appears as a potential novel target to interfere with the macrophage-adipocyte crosstalk in VAT for treating obesity and related metabolic disorders.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INSULIN-RESISTANCE; MICE; FAT; ACCUMULATION; ADIPOCYTES; EXPRESSION; FHL2; NPY; macrophages; adipocytes; MCP-1; thermogenesis; obesity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2024 09:01 |
| Last Modified: | 09 Apr 2024 09:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60710 |
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