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Topical Area: Obesity

Obesity (Poster Session)

(P31-071-23) Browning of Adipose-derived Stromal Cells From db/db mice by Resveratrol

Monday, July 24, 2023
12:45 PM – 1:45 PM ET
Location: Poster Board 293
Disclosure(s):
Xinyun Xu, PhD(c): No relevant financial relationship(s) with ineligible companies to disclose.
Haoying Wu, Phd student: No relevant financial relationship(s) with ineligible companies to disclose.
Mehrnaz Abbasi, PhD: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Obesity, characterized by excessive lipid accumulation in white adipose tissue (WAT), contributes to the development of chronic metabolic diseases, including type 2 diabetes mellitus (T2DM). Browning, in which white adipocytes are converted into beige/brown-like adipocytes, can potentially increase energy expenditure and improve metabolism. Db/db mice with a leptin receptor mutation are a commonly used animal model for severe obesity and T2DM. Trans-resveratrol (RES), a natural polyphenol, has been shown to induce the browning of white adipocytes in diet-induced obesity in mice. This study compares the differences in basal thermogenic gene expression in the subcutaneous WAT and responses to the browning agent RES in both sexes of db/db mice compared to their wild-type (WT) littermate controls.

Methods: Subcutaneous WAT was collected from male and female db/db and WT mice at 10-12 weeks old, and the basal expression of thermogenic genes across genotypes and sexes was compared. Adipose-derived stromal cells (ASCs) were isolated from the subcutaneous WAT and treated with RES at 10 µM, a physiologically achievable dose, for seven days. mRNA expression of thermogenic Ucp1, Pgc1⍺, and white adipocyte-specific marker Igfbp3 was analyzed.

Results: At basal level, within each sex, there were no significant differences in the mRNA expression of Ucp1, Pgc1⍺, and Igfbp3 between db/db and WT mice. However, male mice showed significantly higher Ucp1 mRNA expression, whereas female mice showed higher Pgc1⍺ mRNA expression in both db/db and WT mice. RES significantly upregulated Ucp1 and Pgc1⍺ mRNA expression in ASCs derived from db/db mice regardless of sex. In contrast, RES only promoted Ucp1 mRNA expression in the ASCs derived from WT mice of both sexes.

Conclusions: We found (1) no significant differences in basal mRNA expression of selected key thermogenic genes in the subcutaneous WAT of db/db mice compared to the WT controls;(2) significant sex differences exist in Ucp1 and Pgc1⍺ mRNA expression in the subcutaneous WAT; (3) RES, at an achievable dose, can induce browning of the ASCs derived from db/db mice. These results suggest the utility of RES in inducing browning and improving metabolism in severe obesity and T2DM and underscore the importance of considering sex in studying obesity and browning.

Funding Sources: The study is supported by NIH R15 grant.