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 5

Impacts of UCP1 knockdown on global metabolic functions under an extreme cold condition.

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Impacts of UCP1 knockdown on global metabolic functions under an extreme...
(A) Immunohistological analysis of AAV transduction efficiency. AAV-Gfp– and AAV-shUcp1–transduced eWAT expressed GFP (green). The sections were counter-stained with DAPI (blue). Transduction efficiencies were quantified (n = 4 samples per group, 2-tailed t test). (B) Knockdown efficiency of endogenous UCP1 protein was analyzed by Western blot analysis (n = 6 samples per group, 2-tailed t test). (C) Contingent survival and death of AAV-Gfp– and AAV-shUcp1–transduced mice under –10°C/–20°C (n = 20 mice per group, χ2 test). (D) Metabolic rates of O2 consumption and CO2 production of AAV-Gfp– and AAV-shUcp1–transduced mice in response to norepinephrine (NE) under –10°C/–20°C (n = 5 mice per group). Two-way ANOVA, data represent mean ± SEM. (E) Fasting glucose, fasting insulin, and insulin-tolerance test of AAV-Gfp– and AAV-shUcp1–transduced mice under –10°C/–20°C (n = 10 mice per group). AUC of insulin-tolerance test. *P < 0.05; **P < 0.01; ***P < 0.001. 2-tailed t test for fasting glucose, fasting insulin, and AUC; two-way ANOVA for insulin-tolerance test. Data represent mean ± SEM. Box-and-whisker plots show median (line within box), upper and lower quartile (bounds of box), and minimum and maximum values (bars).