Broussonetia papyrifera Root Bark Extract Exhibits Anti-inflammatory Effects on Adipose Tissue and Improves Insulin Sensitivity Potentially Via AMPK Activation.

Jae Min Lee,Sei Ryang Oh,Yo Han Lee,Sun Sil Choi,Mi Hyeon Park,Jiyoung Park,Hyung Won Ryu,Jang Hyun Choi,Hyunduk Jang,Keon Woo Khim

doi:10.3390/nu12030773

Abstract

The chronic low-grade inflammation in adipose tissue plays a causal role in obesity-induced insulin resistance and its associated pathophysiological consequences. In this study, we investigated the effects of extracts of Broussonetia papyrifera root bark (PRE) and its bioactive components on inflammation and insulin sensitivity. PRE inhibited TNF-α-induced NF-κB transcriptional activity in the NF-κB luciferase assay and pro-inflammatory genes’ expression by blocking phosphorylation of IκB and NF-κB in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-κB phosphorylation and pro-inflammatory genes’ expression. Furthermore, PRE activated AMP-activated protein kinase (AMPK) and reduced lipogenic genes’ expression in both adipose tissue and liver. Finally, we identified broussoflavonol B (BF) and kazinol J (KJ) as bioactive constituents to suppress pro-inflammatory responses via activating AMPK in 3T3-L1 adipocytes. Taken together, these results indicate the therapeutic potential of PRE, especially BF or KJ, in metabolic diseases such as obesity and type 2 diabetes.

Highlights

Inflammation is a protective response against infection, tissue stress, and injury in any tissue and defends and restores physiological functions
A previous study has demonstrated that pro-inflammatory gene expression is elevated in adipose tissue in the early onset of obesity, but in other tissues, such as liver and skeletal muscle, there is no differences in the expression of inflammatory gene expressions [3]
Adipose tissues appear to act as priming tissues that respond to a high-fat diet (HFD) and initiate inflammation in obesity

Summary

Introduction

Inflammation is a protective response against infection, tissue stress, and injury in any tissue and defends and restores physiological functions. Obese adipose tissue produces inflammatory cytokines, including tumor necrosis factor (TNF)-α, monocyte chemokine protein (MCP)-1, and interleukin (IL)-6 [1]. Nutrients 2020, 12, 773 adipose tissue, and other peripheral tissues, such as liver [2]. The accumulation of pro-inflammatory responses in adipose tissue may be one of the causal factors for insulin resistance. A previous study has demonstrated that pro-inflammatory gene expression is elevated in adipose tissue in the early onset of obesity, but in other tissues, such as liver and skeletal muscle, there is no differences in the expression of inflammatory gene expressions [3]. Adipose tissues appear to act as priming tissues that respond to a high-fat diet (HFD) and initiate inflammation in obesity

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Conclusion