adiponectin

(GBP-28, apM1, AdipoQ, Acrp30)

A polypeptide hormone and adipokine, that improves insulin sensitivity (modulates glucose levels) and stimulates fatty acid oxidation.
In humans, it is encoded by the ADIPOQ gene and is produced primarily in adipocytes (in subcutaneous, visceral, and marrow fat tissues) but also in the skeletal and heart muscle cells,endothelial cells, and brain.

(Examples of adipokines)
• leptin
• adiponectin
• resistin
• interleukin-6 (IL-6)
• tissue necrosis factor (TNF)

Low plasma adiponectin levels are associated with obesity, diabetes mellitus type 2, dyslipidemia, and atherosclerosis.
In pregnant women, circulating adiponectin levels decrease correspondingly with insulin sensitivity, and adiponectin levels are low in gestational diabetes.
Circulating adiponectin concentrations increase with anorexia nervosa.

(Receptors for adiponectins)
• adiponectin receptor 1 (AdipoR1): Highly expressed in skeletal muscle.
• adiponectin receptor 2 (AdipoR2): Expressed in the liver (primarily) and skeletal muscle.
• T-cadherin (CDH13): Activates an NFκB signaling pathway, which plays a central role in inflammation and links obesity and vascular disease.
In the hypothalamus, AdipoR1 and AdipoR2 co-localize with the leptin receptor.

Adiponectin exists in blood as a proteolytic cleavage fragment of the globular adiponectin as well as the full-length adiponectin. The monomeric form is undetectable in native conditions.
(Forms of adiponectins)
• globular adiponectin (globular C1q domain of adiponectin): A trimer (mainly). Biologically active.
• full-length adiponectin
- - low-molecular weight (LMW) adiponectin: A homotrimer.
- - middle-molecular weight (MMW) adiponectin: A hexamer.
- - high-molecular weight (HMW) adiponectin: A 12- to 18-mer. The major bioactive isoform contributing to its insulin-sensitizing and cardiovascular protective effects.

Cf. peroxisome proliferator-activated receptor gamma (PPAR-γ)