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Hepatic DsbA‐L protects mice from diet‐induced hepatosteatosis and insulin resistance
Author(s) -
Chen Hongzhi,
Bai Juli,
Dong Feng,
Fang Hezhi,
Zhang Yun,
Meng Wen,
Liu Bilian,
Luo Yan,
Liu Meilian,
Bai Yidong,
AbdulGhani Muhammad A.,
Li Rongxia,
Wu Jiarui,
Zeng Rong,
Zhou Zhiguang,
Dong Lily Q.,
Liu Feng
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600985r
Subject(s) - insulin resistance , dsba , medicine , endocrinology , mitochondrion , type 2 diabetes , chemistry , downregulation and upregulation , insulin , diabetes mellitus , biology , biochemistry , gene , escherichia coli , periplasmic space
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 J. 31, 2314–2326 (2017). www.fasebj.org