Related Experiment Video
Updated: Oct 14, 2025
Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
Published on: March 28, 2013
Withaferin A Promotes White Adipose Browning and Prevents Obesity Through Sympathetic Nerve-Activated Prdm16-FATP1
Bingbing Guo1, Jiarui Liu1, Bingwei Wang1
1Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China.
Abstract:
The increasing prevalence of obesity has resulted in demands for the development of new effective strategies for obesity treatment. Withaferin A (WA) shows a great potential for prevention of obesity by sensitizing leptin signaling in the hypothalamus. However, the mechanism underlying the weight- and adiposity-reducing effects of WA remains to be elucidated. In this study, we report that WA treatment induced white adipose tissue (WAT) browning, elevated energy expenditure, decreased respiratory exchange ratio, and prevented high-fat diet-induced obesity. The sympathetic chemical denervation dampened the WAT browning and also impeded the reduction of adiposity in WA-treated mice. WA markedly upregulated the levels of Prdm16 and FATP1 (Slc27a1) in the inguinal WAT (iWAT), and this was blocked by sympathetic denervation. Prdm16 or FATP1 knockdown in iWAT abrogated the WAT browning-inducing effects of WA and restored the weight gain and adiposity in WA-treated mice. Together, these findings suggest that WA induces WAT browning through the sympathetic nerve-adipose axis, and the adipocytic Prdm16-FATP1 pathway mediates the promotive effects of WA on white adipose browning.
Insights
Withaferin A (WA) promotes obesity treatment by inducing white adipose tissue (WAT) browning. This occurs via the sympathetic nervous system and the Prdm16-FATP1 pathway, increasing energy expenditure and reducing adiposity.
Area of Science:
- Metabolic research
- Obesity research
- Molecular endocrinology
Background:
- Rising obesity rates necessitate novel therapeutic strategies.
- Withaferin A (WA) shows potential in obesity prevention by enhancing leptin signaling.
- The precise mechanisms of WA's weight-reducing effects require further investigation.
Purpose of the Study:
- To elucidate the mechanism by which WA reduces weight and adiposity.
- To investigate WA's effects on white adipose tissue (WAT) browning and energy expenditure.
- To identify the molecular pathways mediating WA's anti-obesity effects.
Main Methods:
- Administration of WA to mice, including those on a high-fat diet.
- Sympathetic chemical denervation to assess the role of the sympathetic nervous system.
- Knockdown of Prdm16 and FATP1 in inguinal WAT (iWAT).
- Measurement of WAT browning, energy expenditure, and adiposity.
Main Results:
- WA treatment induced WAT browning, increased energy expenditure, and prevented diet-induced obesity.
- Sympathetic denervation reduced WA's browning effects and adiposity reduction.
- WA upregulated Prdm16 and FATP1 in iWAT, which was blocked by denervation.
- Prdm16 or FATP1 knockdown negated WA's browning effects and reversed weight gain.
Conclusions:
- WA induces WAT browning through the sympathetic nerve-adipose axis.
- The adipocytic Prdm16-FATP1 pathway is crucial for WA's white adipose browning effects.
- WA represents a potential therapeutic agent for obesity by promoting WAT browning.
