The Role of Chemerin in Metabolic and Cardiovascular Disease: A Literature Review of Its Physiology and Pathology from a Nutritional Perspective

Abstract

Chemerin is a novel adipokine that plays a major role in adipogenesis and lipid metabolism. It also induces inflammation and affects insulin signaling, steroidogenesis and thermogenesis. Consequently, it likely contributes to a variety of metabolic and cardiovascular diseases, including atherosclerosis, diabetes, hypertension and pre-eclampsia. This review describes its origin and receptors, as well as its role in various diseases, and subsequently summarizes how nutrition affects its levels. It concludes that vitamin A, fat, glucose and alcohol generally upregulate chemerin, while omega-3, salt and vitamin D suppress it. Dietary measures rather than drugs acting as chemerin receptor antagonists might become a novel tool to suppress chemerin effects, thereby potentially improving the aforementioned diseases. However, more detailed studies are required to fully understand chemerin regulation.

Keywords: cardiovascular disease; chemerin; metabolic disease; nutrients.

Figure 1

Induction of chemerin synthesis with retinoic acid, the activation of its receptors, and the resulting second messenger cascade. Not only chemerin, but also FAM19A1 and resolvin E1 target these receptors. See text for further details. RARRES2, retinoic acid receptor responder 2; FXR, farnesoid X receptor; RAR, retinoic acid receptor; RXR, retinoid X receptor; PPARγ, peroxisome proliferator-activated receptor γ; SREBP2, sterol regulatory element-binding protein 2; CMKLR1, Chemerin-like receptor 1; CCRL2, CC-motif chemokine receptor-like 2; GPR1, chemerin type 2 receptor; ERK1/2, extracellular signal-regulated kinase 1/2; NFκB, nuclear factor-κB; PI3K, phosphoinositide 3-kinase; AKT, protein kinase B.

Figure 2

Effect of nutrient or diet on chemerin synthesis.

Figure 3

Chemerin-induced vasoconstriction involves both direct effects via its type 1 receptor (CMKLR1) on vascular smooth muscle cells (VSMCs), mediated via cyclic adenosine monophosphate (cAMP) reduction, upregulation of extracellular signal-regulated kinase 1/2 (ERK1/2) and reactive oxygen species (ROS), and indirect effects mediated via activation of the sympathetic nervous system. NO, generated by endothelial NO synthase (eNOS) in endothelial cells (EC), will counteract the effects of chemerin. Data are from references [24,26,28,35,143].

Figure 4

Placental trophoblast chemerin overexpression in mice induces a pre-eclampsia-like syndrome, involving hypertension and proteinuria, combined with diminished trophoblast invasion (by suppressing matrix metalloproteinase (MMP)-2), a disorganized labyrinth layer, and up-regulation of the anti-angiogenic factor soluble Fms-like tyrosine kinase-1 (sFlt-1) and the inflammation markers nuclear factor-κB (NFκB), tumor necrosis factor (TNF)-α and interleukin (IL)-1β, while downregulating vascular endothelial growth factor-a (VEGFa). The disturbed sFlt-1/VEGFa ratio involves the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. Finally, extracellular signal-regulated kinase 1/2 (ERK1/2) upregulation might lead to lipid accumulation. Figure 4 summarizes the findings from references [110,158]. CMKLR1, chemerin-like receptor 1; CCRL2, CC motif chemokine receptor-like 2.