TSH promotes adiposity by inhibiting the browning of white fat

ABSTRACT

Adiposity is caused by an imbalance between energy intake and consumption. Promotion of the browning of white fat increases energy expenditure and could combat adiposity. Thyroid-stimulating hormone (TSH) has been confirmed to positively correlate with adiposity. However, the putative connection between TSH and white adipose browning has never been explored. In this study, we sought to assess the effect of TSH on white adipose tissue browning and energy metabolism. Subclinical hypothyroidism mice, thyroid-specific Tshr-knockout mice injected with TSH, adipocyte-specific and global Tshr-knockout micewere subjected to morphological, physiological, genetic or protein expression analyses and metabolic cages to determine the role of TSH on the browning of white adipose tissue and metabolism. 3T3-L1 and primary SVF cells were used to verify the effects and mechanism of TSH on the browning of white adipocytes. We show that increased circulation TSH level decreases energy expenditure, promotes adiposity, impairs glucose and lipid metabolism. Knockout of Tshr decreases adiposity, increases energy expenditureand markedly promotes the development of beige adipocytesin both epididymal and inguinal subcutaneous white fat via a mechanism that likely involves AMPK/PRDM16/PGC1α. Our results reveal an important role of TSH in regulating energy balance and adiposity by inhibiting the browning of white fat.

KEYWORDS:

• Adiposity
• browning
• TSH
• AMPK
• PRDM16
• PGC1Α

Acknowledgments

Thanks AMERICAN JOURNAL EXPRESS (AJE) for providing language help.

Author contributions

Z.J. conceived and designed the experiments, contributed to the research data and wrote the manuscript; H.W. contributed to the research data; S.M. and C. Y. contributed to the mouse experiments; L.G. reviewed the manuscript; and F.J. and J.Z. conceived and designed the experiments and discussed, reviewed and edited the manuscript.

Disclosure statement

The authors have no competing financial interests to declare.

Consent for publication

Written consent for publication was obtained from all the participants.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation [81400828] and the Natural Science Foundation of Shandong Province [ZR2014HQ057]. This study was also supported by Projects of the Medical and Health Technology Development Program in Shandong Province [2016WS0427] and Shandong Key R&D Program [2017GSF18129].