Regulation of Metabolic Disease-Associated Inflammation by Nutrient Sensors.

Alex S Yamashita,William T Festuccia,Nicolette C Bishop,Fábio S Lira,Thiago Belchior,Barbara Wessner,José C Rosa

doi:10.1155/2018/8261432

Abstract

Visceral obesity is frequently associated with the development of type 2 diabetes (T2D), a highly prevalent chronic disease that features insulin resistance and pancreatic β-cell dysfunction as important hallmarks. Recent evidence indicates that the chronic, low-grade inflammation commonly associated with visceral obesity plays a major role connecting the excessive visceral fat deposition with the development of insulin resistance and pancreatic β-cell dysfunction. Herein, we review the mechanisms by which nutrients modulate obesity-associated inflammation.

Highlights

Visceral obesity, the excessive accumulation of fat in the adipose depots located inside the peritoneal cavity, is a major risk factor for the development of several highly prevalent, chronic diseases, namely, type 2 diabetes (T2D), cardiovascular diseases, and some types of cancer, among others [1, 2]
Deletion of rapamycin-insensitive companion of mTOR (RICTOR) and mechanistic target of rapamycin complex 2 (mTORC2) deficiency in myeloid cells was shown to enhance both polarization of bone marrow-derived macrophages to the M1 profile and the proinflammatory cytokine secretion induced by LPS and other TLR ligands and to reduce the expression of M2-related genes [103]
MTORC2-deficient M2 macrophages were shown to display impaired glucose metabolism and reduced peroxisome proliferator-activated receptor γ (PPARγ) content, mitochondrial biogenesis, and fatty acid oxidation, effects that are mediated by Akt and, at least in part, by the transcriptional factor interferon regulatory factor 4 (IRF4) [119]

Summary

Introduction

The excessive accumulation of fat in the adipose depots located inside the peritoneal cavity, is a major risk factor for the development of several highly prevalent, chronic diseases, namely, type 2 diabetes (T2D), cardiovascular diseases, and some types of cancer, among others [1, 2]. In favor of the notion, that elevated serum BCAA levels are rather a consequence of obesity and insulin resistance, both inflammation and endoplasmic reticulum stress [91], major hallmarks of these diseases, were shown to increase circulating BCAA levels by reducing rates of BCAA oxidation in adipose tissue and by enhancing skeletal muscle protein degradation [83].

Results

Conclusion