title: Blocking Nuclear Factor-Kappa B Protects against Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice.
abstract: Inflammation critically contributes to the development of various metabolic diseases. However, the effects of inhibiting inflammatory signaling on hepatic steatosis and insulin resistance, as well as the underlying mechanisms remain obscure. In the current study, male C57BL/6J mice were fed a chow diet or high-fat diet (HFD) for 8 weeks. HFD-fed mice were respectively treated with p65 siRNA, non-silence control siRNA or vehicle every 4th day for the last 4 weeks. Vehicle-treated (HF) and non-silence siRNA-treated (HFNS) mice displayed overt inflammation, hepatic steatosis and insulin resistance compared with chow-diet-fed (NC) mice. Upon treatment with NF-κB p65 siRNA, HFD-fed (HFPS) mice were protected from hepatic steatosis and insulin resistance. Furthermore, Atg7 and Beclin1 expressions and p-AMPK were increased while p-mTOR was decreased in livers of HFPS mice in relative to HF and HFNS mice. These results suggest a crosslink between NF-κB signaling pathway and liver AMPK/mTOR/autophagy axis in the context of hepatic steatosis and insulin resistance.
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.|Department of Endocrinology, Chengdu First People's Hospital, Chengdu, 610000, China.
authors.forename: Linzheng
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, 77843, United States of America.
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xia
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use*; D000067492:RNAi Therapeutics; D051996:Transcription Factor RelA / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; C498144:Rela protein, mouse; D051996:Transcription Factor RelA