Adipocyte-specific deletion of mTOR inhibits adipose tissue development and causes insulin resistance in mice.
The in vivo role of mechanistic target of rapamycin (mTOR) in the development and function of adipose tissue, especially brown adipose tissue (BAT), is not well understood. Here, we aimed to assess the effect of mTOR (also known as Mtor) knockout on adipose tissues and systemic energy metabolism.



We generated adipocyte-specific mTOR-knockout mice (Adipoq-mTOR) by crossing adiponectin-Cre (Adipoq-Cre) mice with mTOR (flox/flox) mice. The mice were then subjected to morphological, physiological (indirect calorimetry, glucose and insulin tolerance tests) and gene expression analyses to determine the role of mTOR in adipose tissues.



We provide in vivo evidence that mTOR is essential for adipose tissue development and growth. Deletion of mTOR decreased the mass of both BAT and white adipose tissues (WAT) and induced browning of WAT. In addition, ablation of mTOR in adipose tissues caused insulin resistance and fatty liver in the Adipoq-mTOR mice. Furthermore, mTOR was required for adipocyte differentiation in vivo and activation of PPARγ ameliorated the differentiation deficiency of the mTOR-null adipocytes.



Our findings demonstrate that mTOR is a critical regulator of adipogenesis and systemic energy metabolism. Our study provides key insights into the role of mTOR in adipose tissues; such knowledge may facilitate the development of novel strategies with which to treat obesity and related metabolic diseases.
College of Animal Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People's Republic of China. tzshan@zju.edu.cn.|Department of Animal Sciences, Purdue University, 901 West State Street, West Lafayette, IN, 47907, USA. tzshan@zju.edu.cn.
Tizhong
T
Shan
Department of Animal Sciences, Purdue University, 901 West State Street, West Lafayette, IN, 47907, USA.|College of Life Sciences, Xinyang Normal University, Xinyang, People's Republic of China.
Pengpeng
P
Zhang
Department of Animal Sciences, Purdue University, 901 West State Street, West Lafayette, IN, 47907, USA.|College of animal science and technology, Guangxi University, Nanning, People's Republic of China.
Qinyang
Q
Jiang
Department of Animal Sciences, Purdue University, 901 West State Street, West Lafayette, IN, 47907, USA.
Yan
Y
Xiong
College of Animal Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, People's Republic of China.
Yizhen
Y
Wang
Department of Animal Sciences, Purdue University, 901 West State Street, West Lafayette, IN, 47907, USA. skuang@purdue.edu.|Purdue University Center for Cancer Research, West Lafayette, IN 47907, USA. skuang@purdue.edu.
Shihuan
S
Kuang
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D047495:PPAR gamma; D058570:TOR Serine-Threonine Kinases
Adipose; Browning; Insulin resistance; PPARγ; mTOR