Switching harmful visceral fat to beneficial energy combustion improves metabolic dysfunctions
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
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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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 3

Food intake, body weight, BMI, and browning of visceral WAT of HFD-fed obese mice.

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Food intake, body weight, BMI, and browning of visceral WAT of HFD-fed o...
(A) Food intake per week, body weight, and BMI of various temperature-exposed HFD-fed obese mice (n = 15 mice per group, data represent mean ± SEM, one-way ANOVA). (B) Mouse morphology and eWAT morphology. (C) Fat mass of eWAT, s.c. WAT, and iBAT of various HFD-fed obese mice (n = 15 mice per group, data represent mean ± SEM, one-way ANOVA). (D) Contingent survival and death of mice exposed to various temperatures (n = 20 mice per group). (E and F) H&E, UCP1, prohibitin, perilipin A, and endomucin staining of eWAT. Scale bars: 20 μm. (G) Quantification of AC size and UCP1-, prohibitin-, and endomucin-positive signals of eWAT (40 random fields from 8 mice in each group). *P < 0.05; **P < 0.01; ***P < 0.001, one-way ANOVA. Box-and-whisker plots show median (line within box), upper and lower quartile (bounds of box), and minimum and maximum values (bars).