Mammalian Target of Rapamycin Signaling Pathway Regulates Mitochondrial Quality Control of Brown Adipocytes in Mice.

Bahetiyaer Huwatibieke,Lingchao Liu,Wenzhen Yin,Weizhen Zhang,Xinxin Xiang,Yuxin Jin,Jingyan Han,Yin Li

doi:10.3389/fphys.2021.638352

Bahetiyaer Huwatibieke, Lingchao Liu + Show 6 more

Open Access

https://doi.org/10.3389/fphys.2021.638352

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Abstract

The mammalian target of rapamycin (mTOR) is an important protein kinase that senses changes in extracellular and intracellular energy levels and plays a key role in regulating energy metabolism. Brown adipose tissue, which can be converted to white adipose tissue, contains a large number of mitochondria and regulates energy expenditure through thermogenesis. Because obesity is a process of fat accumulation due to chronic excessive energy intake, we attempted to determine whether the mTOR signaling pathway can affect the mitochondrial quality control of brown adipocytes through sensing energy status, thereby regulating brown/white adipocyte transformation. In the present study, through activation or inhibition of mTOR signaling, we detected mitochondrial biogenesis, dynamics, and autophagy-related markers in brown adipocytes. We found that activation of mTOR signaling downregulated the expression of mitochondrial biogenesis, dynamics, and autophagy-relevant markers and inhibited the mitochondrial quality control of brown adipocytes, indicating a phenotypic transformation of brown to white adipocytes. In contrast, inhibition of mTOR signaling upregulated the expression of mitochondrial biogenesis, dynamics, and mitophagy-relevant markers and strengthened mitochondrial quality control, suggesting an inhibition of the phenotypic transformation of brown to white adipocytes. In conclusion, the mTOR signaling pathway plays an important role in modulating the transformation of adipocytes by regulating mitochondrial quality control.

Highlights

Obesity results from a fat accumulation process caused by long-term excess energy intake, which is closely related to the development of “metabolic syndrome,” such as diabetes, hypertension, hyperlipidemia, and atherosclerosis (Kopelman, 2000; Stacchiotti et al, 2014)
The current study suggests that mTORC1- and mTORC2-related signaling is involved in thermogenesis through regulation of lipid metabolism, thermogenic gene expression, and mitochondrial biogenesis and function (Ye et al, 2019)
We investigated the role of the mammalian target of rapamycin (mTOR) signaling pathway in mitochondrial quality control of brown adipocytes and found that mTOR activation inhibits mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy of brown adipocytes, affecting the phenotypic transformation of brown/white adipocytes

Summary

Introduction

Obesity results from a fat accumulation process caused by long-term excess energy intake, which is closely related to the development of “metabolic syndrome,” such as diabetes, hypertension, hyperlipidemia, and atherosclerosis (Kopelman, 2000; Stacchiotti et al, 2014). Adipose tissue is generally divided into two types, white and brown (Soni et al, 2019). White adipose tissue stores excess energy in the form of large monolocular lipid droplets (Cinti, 2005), while brown adipose tissue is rich in mitochondria, with small multilocular lipid droplets (Soni et al, 2019). Brown adipose tissue accelerates energy metabolism and promotes fat consumption. Active brown adipose tissue exists in humans, which can be activated by cold and is negatively associated with obesity. Promotion of brown adipose tissue (BAT) activity or browning of white adipose tissue (WAT) is associated with cold tolerance in vivo, increased energy expenditure, and protection against obesity (Fenzl and Kiefer, 2014)

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