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- Title
Thyrotropin and Obesity: Increased Adipose Triglyceride Content Through Glycerol-3-Phosphate Acyltransferase 3.
- Authors
Ma, Shizhan; Jing, Fei; Xu, Chao; Zhou, Lingyan; Song, Yongfeng; Yu, Chunxiao; Jiang, Dongqing; Gao, Ling; Li, Yujie; Guan, Qingbo; Zhao, Jiajun
- Abstract
Epidemiological evidence indicates that thyrotropin (TSH) is positively correlated with the severity of obesity. However, the mechanism remains unclear. Here, we show that TSH promoted triglyceride (TG) synthesis in differentiated adipocytes in a thyroid hormone-independent manner. Mice with subclinical hypothyroidism, which is characterized by elevated serum TSH but not thyroid hormone levels, demonstrated a 35% increase in the total white adipose mass compared with their wild-type littermates. Interestingly, Tshr KO mice, which had normal thyroid hormone levels after thyroid hormone supplementation, resisted high-fat diet-induced obesity. TSH could directly induce the activity of glycerol-3-phosphate-acyltransferase 3 (GPAT3), the rate-limiting enzyme in TG synthesis, in differentiated 3T3-L1 adipocytes. However, following either the knockdown of Tshr and PPARγ or the constitutive activation of AMPK, the changes to TSH-triggered GPAT3 activity and adipogenesis disappeared. The over-expression of PPARγ or the expression of an AMPK dominant negative mutant reversed the TSH-induced changes. Thus, TSH acted as a previously unrecognized master regulator of adipogenesis, indicating that modification of the AMPK/PPARγ/GPAT3 axis via the TSH receptor might serve as a potential therapeutic target for obesity.
- Subjects
OBESITY genetics; THYROTROPIN regulation; ADIPOSE tissue physiology; ANALYSIS of triglycerides; ACYLTRANSFERASE genetics; PHOSPHATES; CHEMICAL synthesis; GLYCERIN metabolism
- Publication
Scientific Reports, 2015, p7633
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep07633