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adiponectin

Endocrinology / BiochemistryEndocrineAdipose tissueCardiovascularHepaticMusculoskeletal

Summary

Adiponectin is an adipokine secreted by adipocytes that enhances insulin sensitivity, stimulates fatty acid oxidation (via AMPK activation), and has anti-inflammatory and anti-atherogenic effects. Unlike most adipokines, its levels are DECREASED in obesity, insulin resistance, type 2 diabetes, and metabolic syndrome.

Detail

**Source and structure:** Adiponectin (also called Acrp30, AdipoQ) is a ~30 kDa protein hormone produced almost exclusively by adipocytes (white adipose tissue). It circulates as trimers, hexamers, and high-molecular-weight (HMW) multimers; the HMW form is the most biologically active for insulin sensitization. It is one of the most abundant plasma adipokines.

**Receptors and signaling:** Acts through AdipoR1 (predominantly skeletal muscle) and AdipoR2 (predominantly liver), as well as T-cadherin. Receptor binding activates AMP-activated protein kinase (AMPK) and PPAR-alpha, with downstream effects including: - Increased fatty acid oxidation (muscle, liver) - Increased glucose uptake in skeletal muscle - Decreased hepatic gluconeogenesis - Decreased hepatic lipogenesis - Increased insulin sensitivity

**Clinical significance:** - **Inverse relationship with adiposity:** Levels are LOW in obesity (especially visceral fat), insulin resistance, type 2 diabetes, metabolic syndrome, NAFLD, and coronary artery disease. Weight loss increases levels. (Paradoxical: most adipokines such as leptin, resistin, TNF-alpha, and IL-6 are elevated in obesity.) - **Anti-inflammatory:** Reduces TNF-alpha and IL-6 signaling; inhibits macrophage foam cell formation and endothelial adhesion molecule expression, so it is anti-atherogenic. Promotes endothelial NO production. - **Hypoadiponectinemia** is an independent risk factor for T2DM, hypertension, and cardiovascular disease. - **Regulation:** TNF-alpha and other inflammatory cytokines suppress adiponectin. Thiazolidinediones (pioglitazone, rosiglitazone; PPAR-gamma agonists) INCREASE adiponectin expression, which contributes to their insulin-sensitizing effect. - **Sex differences:** Higher in women than men (androgens suppress it).

**High-yield comparison with other adipokines:** - Leptin: satiety signal (acts on arcuate nucleus, inhibits NPY/AgRP, stimulates POMC); high in obesity (leptin resistance); low in leptin-deficiency (ob/ob) obesity. - Resistin: promotes insulin resistance; elevated in obesity. - Adiponectin: insulin-sensitizing; DECREASED in obesity. - Ghrelin (stomach, not adipose): hunger; increased in Prader-Willi syndrome and with sleep deprivation.

**Board pearl:** "Adiponectin goes down as fat goes up." Think: adiponectin = insulin sensitizer, anti-inflammatory, anti-atherogenic, increased by PPAR-gamma agonists (glitazones) and weight loss.

Sources

  • First Aid for the USMLE Step 1 (Endocrine and Biochemistry sections)
  • Harrison's Principles of Internal Medicine, Chapter on Obesity and Metabolic Syndrome
  • Guyton and Hall Textbook of Medical Physiology (Energy balance and adipokines)
  • Robbins & Cotran Pathologic Basis of Disease (Obesity and metabolic syndrome)
  • Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005;26(3):439-451

Reviewed by Medusa editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.