Gene Number: 9370

Location: 3q27.3

Key Functions: Glucose regulation, insulin sensitivity, fatty acid oxidation, anti-inflammatory signaling

The ADIPOQ (adiponectin) gene encodes a secreted protein hormone that is predominantly synthesized by white adipose tissue and circulates abundantly in the bloodstream. Adiponectin acts as a metabolic regulator, bridging the endocrine functions of adipose tissue with systemic energy homeostasis. It plays a central role in glucose metabolism, lipid oxidation, and inflammatory control, thereby linking adipose biology directly to insulin action and cardiovascular health.

At the molecular level, adiponectin exerts its biological effects through two primary receptors—ADIPOR1 and ADIPOR2—which are expressed in metabolically active tissues such as skeletal muscle and liver. Binding of adiponectin to these receptors activates intracellular signaling cascades involving AMP-activated protein kinase (AMPK) and peroxisome proliferator–activated receptor alpha (PPAR-α). These pathways jointly enhance fatty acid oxidation, glucose uptake, and mitochondrial biogenesis, while suppressing hepatic gluconeogenesis. The result is improved insulin sensitivity and lower circulating glucose and lipid levels.

Beyond its metabolic actions, adiponectin possesses potent anti-inflammatory and anti-atherogenic properties. It inhibits the expression of adhesion molecules and pro-inflammatory cytokines (such as TNF-α and IL-6) in endothelial cells and macrophages, reducing vascular inflammation and protecting against atherosclerosis. In cardiomyocytes, adiponectin limits hypertrophy and apoptosis, offering additional cardioprotective effects.

Genetically, polymorphisms in ADIPOQ—such as rs266729, rs1501299, and rs2241766—have been extensively studied for their association with metabolic syndrome, type 2 diabetes, obesity, and coronary artery disease. These variants often lead to reduced circulating adiponectin levels, diminished receptor signaling, and impaired metabolic flexibility. Individuals carrying certain risk alleles exhibit greater insulin resistance, higher body mass index (BMI), and a predisposition to lipid dysregulation. Conversely, higher adiponectin expression correlates with improved glucose tolerance and enhanced cardiovascular resilience.

From a physiological perspective, adiponectin levels are inversely correlated with adiposity—an unusual feature among adipokines. Whereas most adipose-derived hormones (like leptin or resistin) increase with body fat, adiponectin declines as adiposity rises. This inverse relationship helps explain why obesity is accompanied by insulin resistance and chronic low-grade inflammation, as the loss of adiponectin’s protective influence amplifies metabolic stress.

Furthermore, adiponectin acts in concert with other metabolic regulators, such as AMPK, SIRT1, and PPARG, creating a coordinated network that fine-tunes nutrient sensing, mitochondrial efficiency, and energy expenditure. Through this integrated signaling web, adiponectin supports metabolic flexibility—the ability to switch efficiently between carbohydrate and fat utilization.

Clinically, serum adiponectin levels serve as a biomarker of metabolic health, predictive of type 2 diabetes onset, cardiovascular risk, and therapeutic response to insulin-sensitizing agents like thiazolidinediones (PPARγ agonists). These drugs can increase adiponectin expression, restoring its beneficial metabolic and vascular functions.

In summary, ADIPOQ is a cornerstone of metabolic regulation, translating adipose tissue signals into systemic effects that preserve energy balance, vascular health, and insulin sensitivity. Genetic and environmental factors that suppress adiponectin expression or function contribute directly to the pathogenesis of metabolic syndrome, making ADIPOQ both a critical biomarker and a potential therapeutic target in the fight against obesity-related disease.