Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2017 Jun

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Hepatic insulin resistance and hepatosteatosis in diet-induced obesity are associated with various metabolic diseases, yet the underlying mechanisms remain to be fully elucidated. Here we show that the expression levels of the disulfide-bond A oxidoreductase-like protein (DsbA-L) are significantly reduced in the liver of obese mice and humans. Liver-specific knockout or adenovirus-mediated overexpression of DsbA-L exacerbates or alleviates, respectively, high-fat diet-induced mitochondrial dysfunction, hepatosteatosis, and insulin resistance in mice. Mechanistically, we found that DsbA-L is localized in mitochondria and that its deficiency is associated with impairment of maximum respiratory capacity, elevated cellular oxidative stress, and increased JNK activity. Our results identify DsbA-L as a critical regulator of mitochondrial function, and its down-regulation in the liver may contribute to obesity-induced hepatosteatosis and whole body insulin resistance.-Chen, H., Bai, J., Dong, F., Fang, H., Zhang, Y., Meng, W., Liu, B., Luo, Y., Liu, M., Bai, Y., Abdul-Ghani, M. A., Li, R., Wu, J., Zeng, R., Zhou, Z., Dong, L. Q., Liu, F. Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance. © FASEB.

Citation

Hongzhi Chen, Juli Bai, Feng Dong, Hezhi Fang, Yun Zhang, Wen Meng, Bilian Liu, Yan Luo, Meilian Liu, Yidong Bai, Muhammad A Abdul-Ghani, Rongxia Li, Jiarui Wu, Rong Zeng, Zhiguang Zhou, Lily Q Dong, Feng Liu. Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2017 Jun;31(6):2314-2326