Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions
Xiaoyan Yang, … , Yun Zhang, Yihai Cao
Xiaoyan Yang, … , Yun Zhang, Yihai Cao
Published February 23, 2017
Citation Information: JCI Insight. 2017;2(4):e89044. https://doi.org/10.1172/jci.insight.89044.
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Research Article Metabolism

Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions

Abstract

Visceral fat is considered the genuine and harmful white adipose tissue (WAT) that is associated to development of metabolic disorders, cardiovascular disease, and cancer. Here, we present a new concept to turn the harmful visceral fat into a beneficial energy consumption depot, which is beneficial for improvement of metabolic dysfunctions in obese mice. We show that low temperature–dependent browning of visceral fat caused decreased adipose weight, total body weight, and body mass index, despite increased food intake. In high-fat diet–fed mice, low temperature exposure improved browning of visceral fat, global metabolism via nonshivering thermogenesis, insulin sensitivity, and hepatic steatosis. Genome-wide expression profiling showed upregulation of WAT browning–related genes including Cidea and Dio2. Conversely, Prdm16 was unchanged in healthy mice or was downregulated in obese mice. Surgical removal of visceral fat and genetic knockdown of UCP1 in epididymal fat largely ablated low temperature–increased global thermogenesis and resulted in the death of most mice. Thus, browning of visceral fat may be a compensatory heating mechanism that could provide a novel therapeutic strategy for treating visceral fat–associated obesity and diabetes.

Authors

Xiaoyan Yang, Wenhai Sui, Meng Zhang, Mei Dong, Sharon Lim, Takahiro Seki, Ziheng Guo, Carina Fischer, Huixia Lu, Cheng Zhang, Jianmin Yang, Meng Zhang, Yangang Wang, Caixia Cao, Yanyan Gao, Xingguo Zhao, Meili Sun, Yuping Sun, Rujie Zhuang, Nilesh J. Samani, Yun Zhang, Yihai Cao

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Figure 8

Schematic diagram of successive activation of defensive mechanisms against decreasing environmental cold.

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Schematic diagram of successive activation of defensive mechanisms again...
Under mild cold such as 4°C exposure, activation of the BAT-nonshivering thermogenesis and modest browning of s.c. WAT are sufficient to maintain core body temperature. However, visceral WAT remains thermogenically inactive. Further decreased environmental temperature — to –10°C, for example — enhances browning of s.c. WAT and triggers modest browning of visceral fat to generate nonshivering heat. With extreme cold such as –10°C/–20°C, browning of visceral fat markedly contributes to nonshivering thermogenesis to main core body temperature. Additionally, browning of visceral fat increases insulin sensitivity and improves liver steatosis in obese mice.