# Effects of Resveratrol on Browning and Insulin Signaling in Primary Murine Adipocytes: Modulation by Sex and Diabetic Status

## TL;DR

Resveratrol promotes browning of fat cells and improves insulin signaling, but its effects vary based on sex and diabetes status in mice.

## Contribution

This study reveals that sex and diabetic status modulate resveratrol's effects on browning and insulin signaling in adipocytes.

## Key findings

- Resveratrol increased Pgc1α and Ucp1 mRNA expression and mitochondrial proton leak in both WT and db/db ADSCs.
- Resveratrol enhanced insulin-induced AKT phosphorylation across all groups of ADSCs.
- Female diabetic mice showed distinct responses to resveratrol compared to WT or male mice.

## Abstract

Background: Excess accumulation of white adipose tissue is linked to the development of obesity and type 2 diabetes, both of which are associated with systemic metabolic dysfunction. One promising approach is to convert white adipocytes into beige adipocytes, which have greater thermogenic potential and improved insulin sensitivity. Trans-resveratrol (RES), a polyphenolic compound known to have multiple metabolic benefits, has been reported to promote browning of adipocytes and improve insulin signaling; however, it is unclear whether sex and diabetic status modify RES’s effects. Methods: We evaluated the ability of RES to induce browning and increase insulin sensitivity in adipose-derived stromal cells (ADSCs) derived from diabetic db/db mice and explored the extent to which these responses are modulated by sex and diabetic status. Subcutaneous ADSCs were isolated from wildtype (WT) and diabetic (db/db) male and female mice and then treated with RES during beige adipocyte differentiation. Results: RES enhanced the expression of Pgc1α and Ucp1 mRNA and increased mitochondrial proton leak in ADSCs of both WT and db/db mice. RES also enhanced insulin-induced AKT phosphorylation in all groups of ADSCs. Notably, the effects of RES on browning and insulin signaling were influenced by the sex and diabetic status of the mice, as ADSCs from female diabetic mice responded differently compared with those from their WT or male counterparts. Conclusions: These findings highlight the importance of considering sex and diabetic status when developing browning strategies to target obesity and type 2 diabetes.