Adiponectin

Discovery

Mouse adiponectin cDNA was cloned from mouse 3T3-L1 cells and called adipocyte complement-related protein of 30kDa (Acrp30) in 1995.In 1996, human adiponectin cDNA was first cloned from adipose tissues by Matsuzawa, who called it adipose most abundant gene transcript 1 (apM1).Adiponectin protein was identified from human plasma in 1996.

Tissue distribution of mRNA

In mammals, Adipoq is mainly expressed in the white and brown adipose tissues. In fish, adipoq is expressed in the liver, adipose tissue, muscle, and brain.

Regulation of synthesis and release

Plasma adiponectin levels are decreased in obesity and diabetes. Adiponectin gene expression is activated by peroxisome proliferator-activated receptor (PPAR) γ, C/EBPs, nuclear factor Y, sterol-regulatory-elementbinding protein (SREBP)-1c, SIRT1, and Foxo1, whereas it is inhibited by tumor necrosis factor (TNF)- α, IL-6, and NFATc4.Insulin and PPARγ stimulate adiponectin secretion via the PI3K pathway.

Clinical implications

Adiponectin improves several dysfunctions such as insulin resistance, hyperlipidemia, hypertension, arteriosclerosis, and nonalcoholic steatohepatitis (NASH). In addition, the plasma adiponectin concentrations were decreased in patients with lifestyle-related diseases and the metabolic syndrome associated with obesity. Thus, adiponectin has a crucial role in diabetes and other metabolic syndromes.

Description

Adiponectin is a cytokine produced by adipocytes and is termed an “ adipokine.” Adiponectin functions as an insulin sensitizer. Downregulation of adiponectin receptors and low levels of adiponectin have been associated with obesity-linked insulin resistance. Exercise and dietary changes have been shown to raise low levels of adiponectin in obese adolescents. Additionally, sarpogrelate hydrochloride, a 5-HT2A antagonist, elevates low adiponectin levels and normalizes other factors associated with vascular changes seen in type 2 diabetes.

Enzyme inhibitor

This 244-residue anti-diabetic hormone (MWmonomer = 30 kDa; Symbol: Ad) is a adipocyte-derived polypeptide that regulates energy homeostasis and glucose and lipid metabolism, mainly by increasing the insulin responsiveness of susceptible cells and by stimulating the phosphorylation/activation of the 5'-AMP-activated protein kinase, or AMPK. Adiponectin circulates in human plasma mainly as a 180-kDa middle molecular weight (MMW) hexamer and a high molecular weight (HMW) multimer of approximately 360 kDa. It has four topologically distinct regions: a short signal sequence targeting the hormone for secretion; a short species-variant region; a 65-residue region resembling collagens; and a globular domain. This adipokine, which bears similarities in domain structure to the complement protein C1q, is processed into at least three homomeric complexes, trimer, hexamer, and a high-molecularweight (HMW) octadecamer. In skeletal muscle. AMPK is stimulated with globular and full-length Ad, whereas AMPK is only stimulated by fulllength Ad in liver. Ad stimulates phosphorylation of acetyl coenzyme A carboxylase (ACC), fatty-acid oxidation, glucose uptake and lactate production in myocytes, phosphorylation of ACC and reduction of molecules involved in gluconeogenesis in the liver, and reduction of glucose levels in vivo. Inhibition of AMPK activation (See Dominant Negative Mutants) blocks each of these effects, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK.