Resistin Activates p65 Pathway and Reduces Glycogen Content through Keratin 8

Fengyun Wen,Amin Rajesh,Yanling Wu,Haipeng Shia,Qiao Xia,Zaiqing Yang,Hui Zhang,Yi Yang

doi:10.1155/2020/9767926

Abstract

Resistin is associated with metabolic syndrome and inflammatory conditions. Many studies have suggested that resistin inhibits the accumulation of glycogen; however, the exact mechanisms of resistin-induced decrease in glycogen content remain unclear. Keratin 8 is a typical epithelial intermediate filament protein, but numerous studies suggest a vital role of K8 in glucose metabolism. However, it is still not known whether K8 participates in the mediation of resistin-induced reduction of cellular glycogen accumulation. In this study, we found that resistin upregulated expression of the p65 subunit of NF-κB, which led to the promotion of K8 transcriptional expression; in turn, the expression of K8 inhibited glycogen accumulation in HepG2 cells.

Highlights

Resistin is one of the important cytokines secreted by adipocytes
Periodic acid-Schiff (PAS) staining was used to assess the glycogen content directly. Both PAS staining and measurement of the glycogen content showed that the glycogen content was significantly decreased in the livers of resistin-treated mice compared with controls (Figures 1(a) and 1(b))
Deletion of K8/K18 in normal and cancerous mouse hepatic cells promotes insulin-mediated glucose uptake [28], suggesting that keratin plays a role in metabolism. e regulatory role of keratin in resistin-mediated glycogen accumulation is the basis of this study

Summary

Introduction

Resistin is one of the important cytokines secreted by adipocytes. It was discovered in 2001 [1] and regarded as the link between obesity and type II diabetes mellitus (T2DM). Resistin is expressed at higher levels in obese humans and mice than in lean controls [2, 3]. Treatment with recombinant mouse resistin impaired the glucose tolerance and activity of insulin and induced hepatic insulin resistance [4]. Recombinant murine resistin significantly decreased glycogen content by decreasing the level of phosphorylated GSK-3β at Ser 9, leading to impaired hepatic insulin action [5]. Many studies have attempted to clarify the mechanism of resistin-induced decrease in glycogen content, the relationship between resistin and glycogen remains unclear

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