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

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.

Identification of MAP3K4 as a novel regulation factor of hepatic lipid metabolism in non-alcoholic fatty liver disease

“…FABP4, which located in cytoplasm of adipocyte, enhanced lipolysis by interacting with hormone-sensitive lipase [ 32 , 50 ]. Inhibition of SERPINE1 reduced hepatic expression levels of PCSK9, which is well acknowledged as a regulator of lipid metabolism by impairing receptor-mediated low-density lipoprotein cholesterol (LDL-C) clearance [ 31 , 51 ].…”

“…Through interference experiments in vitro, our results indicated that MAP3K4 might be involved in the biogenesis of LDs by regulating the phosphorylation of JNK and cPLA2 in NAFLD. FABP4, which located in cytoplasm of adipocyte, enhanced lipolysis by interacting with hormone-sensitive lipase [32,50]. Inhibition of SERPINE1 reduced hepatic expression levels of PCSK9, which is well acknowledged as a regulator of lipid metabolism by impairing receptormediated low-density lipoprotein cholesterol (LDL-C) clearance [31,51].…”

Circulating Ism1 Reduces the Risk of Type 2 Diabetes but not Diabetes-Associated NAFLD

“…The biologically active adipokines secreted by adipose tissue have been frequently reported due to their main role in regulating metabolism, inflammation and glycolipid homeostasis to protect individuals from metabolic diseases onset ( 24 , 25 ). So far, more than 600 adipokines have been proposed and the search for novel adipokines as biomarkers was still a hot topic ( 24 ).…”

Editorial: Functional Profile of the Lipocalin Protein Family

“…This Research Topic highlights yet another function also predicted to be ancestral in the family: regulation of barriers, so important for biological compartments protection [e.g., regulation of endothelial barriers to the passage of immune system cells by AGP ( Ruiz ), Gd or ApoM ( Frances et al, 2021 ; Yao Mattisson and Christoffersen, 2021 ; Penn et al ) or the antagonistic roles of C8G and Lcn2 in preventing or promoting blood-brain-barrier disruption ( Frances et al, 2021 ; Kim et al, 2021 )]. Furthermore, many Lipocalins share functions dealing with the maintenance, composition and redox state of the most basic barriers of all: cellular membranes, with special attention to plasma and lysosomal membranes [ApoD, AGP, A1M, Gd ( Bergwik et al ; Ruiz ; Sanchez and Ganfornina ; Sawyer )] vital for cell survival-death fates.…”