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

• Published in: PLoS biology Vol. 18; no. 3; p. e3000688
• Main Authors: Xia, Bo, Shi, Xiao Chen, Xie, Bao Cai, Zhu, Meng Qing, Chen, Yan, Chu, Xin Yi, Cai, Guo He, Liu, Min, Yang, Shi Zhen, Mitchell, Grant A, Pang, Wei Jun, Wu, Jiang Wei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.03.2020; Public Library of Science (PLoS)
• Subjects: Activation; Adipocytes; Adipose tissue; Adipose tissue (brown); Age; Animal sciences; Animal tissues; Biological activity; Biology and Life Sciences; Body composition; Body fat; Body weight; Body weight gain; Browning; Cancer; Diabetes mellitus; Diet; Energy expenditure; Fatty liver; Food; Gene expression; Genetics; Health problems; High fat diet; Homeostasis; Hyperglycemia; Inflammation; Insulin resistance; Intestinal microflora; Investigations; Laboratories; Liver cancer; Medicine and Health Sciences; Metabolites; Microflora; Muscle function; Musculoskeletal system; Obesity; Propylthiouracil; Research and Analysis Methods; Therapeutic applications; Thermogenesis; Thyroid; Thyroid gland; Thyroid hormones; Thyroxine; Triiodothyronine; Zoology; China
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3000688

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.