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

Hongzhi Chen, Juli Bai, Feng Dong, Hezhi Fang, Yun Zhang, Wen Meng, Bilian Liu, Yan Luo, Meilian Liu, Yidong Bai, Muhammad Abdulghani, Rongxia Li, Jiarui Wu, Rong Zeng, Zhiguang Zhou, Lily Q. Dong, Feng Liu

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10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2314-2326
Number of pages13
JournalFASEB Journal
Volume31
Issue number6
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • Mitochondria
  • NAFLD
  • Oxidative stress

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    Chen, H., Bai, J., Dong, F., Fang, H., Zhang, Y., Meng, W., Liu, B., Luo, Y., Liu, M., Bai, Y., Abdulghani, M., Li, R., Wu, J., Zeng, R., Zhou, Z., Dong, L. Q., & Liu, F. (2017). Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance. FASEB Journal, 31(6), 2314-2326. https://doi.org/10.1096/fj.201600985R