Urolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice.

Abstract

Obesity leads to multiple health problems, including diabetes, fatty liver, and even cancer. Here, we report that urolithin A (UA), a gut-microflora-derived metabolite of pomegranate ellagitannins (ETs), prevents diet-induced obesity and metabolic dysfunctions in mice without causing adverse effects. UA treatment increases energy expenditure (EE) by enhancing thermogenesis in brown adipose tissue (BAT) and inducing browning of white adipose tissue (WAT). Mechanistically, UA-mediated increased thermogenesis is caused by an elevation of triiodothyronine (T3) levels in BAT and inguinal fat depots. This is also confirmed in UA-treated white and brown adipocytes. Consistent with this mechanism, UA loses its beneficial effects on activation of BAT, browning of white fat, body weight control, and glucose homeostasis when thyroid hormone (TH) production is blocked by its inhibitor, propylthiouracil (PTU). Conversely, administration of exogenous tetraiodothyronine (T4) to PTU-treated mice restores UA-induced activation of BAT and browning of white fat and its preventive role on high-fat diet (HFD)-induced weight gain. Together, these results suggest that UA is a potent antiobesity agent with potential for human clinical applications.

• Authors: Bo Xia, Xiao Chen Shi, Bao Cai Xie, Meng Qing Zhu, Yan Chen, Xin Yi Chu, Guo He Cai, Min Liu, Shi Zhen Yang, Grant A Mitchell, Wei Jun Pang, Jiang Wei Wu
• Journal: PLoS biology (PLoS Biol) Vol. 18 Issue 3 Pg. e3000688 (03 2020) ISSN: 1545-7885 [Electronic] United States
• PMID: 32218572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Obesity Agents
• Coumarins
• Triiodothyronine
• 3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
• Propylthiouracil

Topics

• Adipocytes, Brown (drug effects, metabolism)
• Adipocytes, White (drug effects, metabolism)
• Adipose Tissue, Brown (metabolism)
• Adipose Tissue, White (metabolism)
• Animals
• Anti-Obesity Agents (therapeutic use)
• Coumarins (therapeutic use)
• Diet, High-Fat (adverse effects)
• Energy Metabolism (drug effects)
• Fatty Liver (prevention & control)
• Glucose Intolerance (prevention & control)
• Insulin Resistance
• Maillard Reaction
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Obesity (metabolism, prevention & control)
• Propylthiouracil (toxicity)
• Thermogenesis
• Triiodothyronine (antagonists & inhibitors, metabolism)
• Weight Gain (drug effects)