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: Tianshu Zeng, Jing Zhou, Linzheng He, Juan Zheng, Lulu Chen, Chaodong Wu, Wenfang Xia
• Journal: PloS one (PLoS One) Vol. 11 Issue 3 Pg. e0149677 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 26930600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Rela protein, mouse
• Transcription Factor RelA

Topics

• Animals
• Diet, High-Fat (adverse effects)
• Fatty Liver (etiology, genetics, pathology, prevention & control)
• Insulin Resistance
• Liver (metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• RNA, Small Interfering (genetics, therapeutic use)
• RNAi Therapeutics
• Transcription Factor RelA (genetics)