title: Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance.
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.-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.
authors.affiliation: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Disease, Second Xiangya Hospital, Central South University, Changsha, China.|Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Disease, Second Xiangya Hospital, Central South University, Changsha, China.|Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Juli
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Dong
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Hezhi
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Disease, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Disease, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Meng
authors.affiliation: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Disease, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Bilian
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Disease, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Disease, Second Xiangya Hospital, Central South University, Changsha, China.|Department of Biochemistry and Molecular Biology, University of New Mexico Health Science Center, Albuquerque, New Mexico, USA.
authors.forename: Meilian
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Abdul-Ghani
authors.affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Rongxia
authors.initials: R
authors.lastname: Li
authors.affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Wu
authors.affiliation: Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.affiliation: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Disease, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Lily Q
authors.initials: LQ
authors.lastname: Dong
authors.affiliation: Department of Metabolism and Endocrinology, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Disease, Second Xiangya Hospital, Central South University, Changsha, China; liuf@uthscsa.edu.|Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas, USA.|Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects*; D005234:Fatty Liver / Q000139:chemically induced*; D015971:Gene Expression Regulation, Enzymologic; D015309:Glucose Clamp Technique; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000378:metabolism; D018384:Oxidative Stress; D010101:Oxygen Consumption
chemical_list: D004041:Dietary Fats; D000255:Adenosine Triphosphate; D005982:Glutathione Transferase; C000622477:disulfide-bond A oxidoreductase-like protein DsbA-L, mouse
keywords: NAFLD; mitochondria; oxidative stress