TY - JOUR
T1 - Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance
AU - Chen, Hongzhi
AU - Bai, Juli
AU - Dong, Feng
AU - Fang, Hezhi
AU - Zhang, Yun
AU - Meng, Wen
AU - Liu, Bilian
AU - Luo, Yan
AU - Liu, Meilian
AU - Bai, Yidong
AU - Abdulghani, Muhammad
AU - Li, Rongxia
AU - Wu, Jiarui
AU - Zeng, Rong
AU - Zhou, Zhiguang
AU - Dong, Lily Q.
AU - Liu, Feng
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
KW - Mitochondria
KW - NAFLD
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85020313214&partnerID=8YFLogxK
U2 - 10.1096/fj.201600985R
DO - 10.1096/fj.201600985R
M3 - Article
C2 - 28232481
AN - SCOPUS:85020313214
VL - 31
SP - 2314
EP - 2326
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 6
ER -