Adipose-Derived Lipid-Binding Proteins: The Good, the Bad and the Metabolic Diseases

Laurie Frances,Nathalie Viguerie,Geneviève Tavernier

doi:10.3390/ijms221910460

Abstract

Adipose tissue releases a large range of bioactive factors called adipokines, many of which are involved in inflammation, glucose homeostasis and lipid metabolism. Under pathological conditions such as obesity, most of the adipokines are upregulated and considered as deleterious, due to their pro-inflammatory, pro-atherosclerotic or pro-diabetic properties, while only a few are downregulated and would be designated as beneficial adipokines, thanks to their counteracting properties against the onset of comorbidities. This review focuses on six adipose-derived lipid-binding proteins that have emerged as key factors in the development of obesity and diabetes: Retinol binding protein 4 (RBP4), Fatty acid binding protein 4 (FABP4), Apolipoprotein D (APOD), Lipocalin-2 (LCN2), Lipocalin-14 (LCN14) and Apolipoprotein M (APOM). These proteins share structural homology and capacity to bind small hydrophobic molecules but display opposite effects on glucose and lipid metabolism. RBP4 and FABP4 are positively associated with metabolic syndrome, while APOD and LCN2 are ubiquitously expressed proteins with deleterious or beneficial effects, depending on their anatomical site of expression. LCN14 and APOM have been recently identified as adipokines associated with healthy metabolism. Recent findings on these lipid-binding proteins exhibiting detrimental or protective roles in human and murine metabolism and their involvement in metabolic diseases are also discussed.

Highlights

Plasma level and mRNA expression of LCN2 in liver and adipose tissue are higher in obese and diabetic subjects compared with lean individuals [80,82,83]
Fatty acid binding protein 4 (FABP4) which improve insulin sensitivity or attenuate inflammation [120,121], while others have developed novel small inhibiting molecules which stick in FABP4 hydrophobic pocket as molecular lures and prevent its effects [122,123]
Adipose tissue secretes a large range of bioactive molecules, including lipids

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Mice overexpressing human or murine RBP4 in adipocytes and fed with HFD are more prone to develop obesity, insulin resistance and hepatic steatosis than wildtype littermates [28,29] These mice have higher levels of inflammatory markers like tumor necrosis factor α (TNFα) [29]. A recent study focusing on type 1 diabetic patients revealed that low FABP4 plasma levels, due to a functional, low-expression variant in the gene promoter, was associated with a 2.4-fold higher risk of cardiovascular disease [40]. Plasma level and mRNA expression of LCN2 in liver and adipose tissue are higher in obese and diabetic subjects compared with lean individuals [80,82,83]. S1P or is by itself a beneficial cardiometabolic adipokine is still a matter of debate, the latter being more and more considered

Clinical Perspectives

Conclusions and Perspectives