The Role of Adiponectin and ADIPOQ Variation in Metabolic Syndrome: A Narrative Review

Abstract

Metabolic syndrome (MetS), a significant global health concern, is characterized as a cluster of metabolic abnormalities that elevate the risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Adiponectin, an adipokine secreted by adipose tissue, plays a crucial role in regulating glucose and lipid homeostasis while exhibiting protective effects against vascular alterations. Single-nucleotide variants (SNVs) in the ADIPOQ gene have significantly affected circulating adiponectin levels and metabolic parameters. This narrative review examines current evidence on the relationship between adiponectin, ADIPOQ gene variants, and metabolic syndrome. The findings indicate that lower adiponectin levels are associated with an increased risk of metabolic syndrome components, including elevated triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), and fasting glucose levels. In conclusion, adiponectin emerges as a key regulator of metabolic homeostasis, with SNVs in the ADIPOQ gene correlating with the development of metabolic-related complications.

Keywords: ADIPOQ gene; adiponectin; metabolic syndrome; obesity; single-nucleotide variants.

Figure 1

The diagram illustrates the pleiotropic effects of adiponectin on glucose and lipid metabolism and anti-inflammatory actions. In glucose metabolism, adiponectin enhances insulin sensitivity via adenosine monophosphate-activated protein kinase (AMPK) and proliferator-activated receptor-alpha (PPAR-α) activation, promotes glucose transporter-4 (GLUT-4) translocation to increase glucose uptake, and inhibits gluconeogenic enzymes—glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK)—to reduce hepatic glucose production. In lipid metabolism, it stimulates fatty acid (FFA) oxidation through acetyl-CoA carboxylase (ACC) inhibition and carnitine palmitoyltransferase 1 (CPT-1) activation and enhances lipid transport/utilization by increasing cluster of differentiation 36 (CD-36), acyl-CoA oxidase, and uncoupling protein 2 (UCP-2). Adiponectin also elevates HDL-C levels via increased hepatic apolipoprotein AI (ApoA-I), ATP-binding cassette transporter A1 (ABCA1), liver X receptor alpha (LXRα), and peroxisome proliferator-activated receptor gamma (PPARγ) expression. Finally, its anti-inflammatory effects are mediated by suppression of pro-inflammatory cytokines: tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and reduction in oxidative/nitrative stress through of nitric oxide synthase (iNOS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.

Figure 2

Bipartite network illustrating associations between ADIPOQ gene SNVs (blue nodes) and metabolic phenotypes (light pink nodes): BMI, HDL-C, and T2DM. Edge color and thickness reflect the strength of association based on literature evidence: Black edges represent more consistent findings, while gray edges indicate less consistent or preliminary associations. Node sizes distinguish SNVs from phenotypes.

Figure 3

Bipartite network illustrating associations between ADIPOQ gene SNVs (blue nodes) and metabolic phenotypes (light green nodes): glucose uptake, lipid oxidation, and anti-inflammatory effects. Edge color and width indicate the presence or absence of documented effects based on literature: Black edges represent SNVs with reported impact; red edges indicate no documented association. Node size differentiates SNVs and phenotypes.