Adipocyte Ceramides-The Nexus of Inflammation and Metabolic Disease.

Bhagirath Chaurasia,Chad Lamar Talbot,Scott A Summers

doi:10.3389/fimmu.2020.576347

Bhagirath Chaurasia, Chad Lamar Talbot + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2020.576347

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Abstract

Adipose depots are heterogeneous tissues that store and sense fuel levels. Through the secretion of lipids, cytokines, and protein hormones (adipokines), they communicate with other organ systems, informing them of the organism's nutritional status. The adipose tissues include diverse types of adipocytes (white, beige, and brown) distinguished by the number/size of lipid droplets, mitochondrial density, and thermogenic capacity. Moreover, they include a spectrum of immune cells that modulate metabolic activity and tissue remodeling. The unique characteristics and interplay of these cells control the production of ceramides, a class of nutrient signals derived from fat and protein metabolism that modulate adipocyte function to regulate glucose and lipid metabolism. The excessive accumulation of ceramides contributes to the adipose tissue inflammation and dysfunction that underlies cardiometabolic disease. Herein we review findings on this important class of lipid species and discuss their role at the convergence point that links overnutrition/inflammation to key features of the metabolic syndrome.

Highlights

Obesity increases one’s risk for metabolic diseases such as diabetes, coronary artery disease, non-alcoholic steatohepatitis, and heart failure
Ablation of toll-like receptor (TLR)-4 in mice reduces ceramides, and even prevents their synthesis in models of lipid oversupply [77]. These findings indicate that TLR-4 enhances ceramide production and reveal the interplay between TLR-4 and ceramides in the metabolic dysfunction that accompanies obesity
Inflammation has long been known to be a hallmark of obesity, owing to the recruitment of macrophages to adipose depots and the enhancement of TLR-4 signaling by saturated fatty acids

Summary

INTRODUCTION

Obesity increases one’s risk for metabolic diseases such as diabetes, coronary artery disease, non-alcoholic steatohepatitis, and heart failure. In addition to being major fuel reservoirs (e.g., triglycerides), have important roles in the regulation of nutrient storage Sphingolipids such as ceramides are metabolic signals that accumulate in obesity and trigger evolutionarily conserved cellular responses to lipid overload [9]. Such mechanisms include inhibiting the uptake of glucose and amino acids, leading to the preferential utilization of free fatty acids (FFAs) for energy; slowing rates of triglyceride lipolysis; and impairing mitochondrial respiration [9]. Studies in mice reveal that inhibition of ceramide synthesis resolves hepatic steatosis and improves insulin-stimulated glucose disposal to slow the progression of cardiometabolic diseases [11] These ceramide-lowering interventions alter adipose tissue metabolism and morphology, enhancing glucose utilization, and energy expenditure. We will discuss the potential therapeutic approaches for targeting ceramides to reduce inflammation and improve adipose health

EXCESS FREE FATTY ACIDS INDUCE METABOLIC DISORDERS

PATHWAYS CONTROLLING CERAMIDE SYNTHESIS AND METABOLISM

Adiponectin Receptors Are Ligand Activated Ceramidases

CONVERGENCE OF ADIPOSE CERAMIDES AND INFLAMMATION TO CONTROL INSULIN RESISTANCE

CONCLUSION