Reactome | ADIPOQ trimer binds ADIPOR dimers

ADIPOQ trimer binds ADIPOR dimers

Stable Identifier

R-HSA-8848663

Type

Reaction [transition]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

ReviewStatus

5/5

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Adipokines are a group of over 600 bioactive molecules produced by adipose tissue that acts as paracrine and endocrine hormones. These molecules are important in the regulation of diverse processes including appetite control, fat distribution, inflammation, blood pressure, hemostasis and endothelial function. Adipokines may present anti and proinflammatory effects. Cardiovascular diseases (CVDs) can be one of the most important causes of death in diabetics and diabetes can in turn increase the risk of cardiovascular events. Obesity is a chronic condition. It is associated with overproduction of inflammatory adipokines by adipose tissue, which may link obesity to CVD and diabetes (Freitas Lima et al. 2015).

Adiponectin (ADIPOQ, also known as 30-kDa adipocyte complement-related protein ACRP30) is an adipocyte-derived hormone that acts as an antidiabetic and anti-atherogenic adipokine. ADIPOQ blood levels are decreased under conditions of obesity, insulin resistance and type 2 diabetes. ADIPOQ can form a wide range of multimers from trimers to high molecular weight (HMW) multimers (Waki et al. 2003). The trimeric form is shown here. Through binding adiponectin receptor proteins 1 and 2 (ADIPOR1 and 2), ADIPOQ trimer stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose and fatty-acid utilisation. ADIPOR1 is abundantly expressed in skeletal muscle, whereas ADIPOR2 is predominantly expressed in the liver (Yamauchi et al. 2003). ADIPORs are thought to function as homo- or hetero-multimers. For simplicity, the combinations annotated here are shown as homodimers. Although ADIPOR1 and 2 are predicted to contain seven transmembrane domains, they are structurally, topologically and functionally distinct from GPCRs.

Literature References

PubMed ID	Title	Journal	Year
12878598	Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin Waki, H, Yamauchi, T, Kamon, J, Ito, Y, Uchida, S, Kita, S, Hara, K, Hada, Y, Vasseur, F, Froguel, P, Kimura, S, Nagai, R, Kadowaki, T	J. Biol. Chem.	2003
12802337	Cloning of adiponectin receptors that mediate antidiabetic metabolic effects Yamauchi, T, Kamon, J, Ito, Y, Tsuchida, A, Yokomizo, T, Kita, S, Sugiyama, T, Miyagishi, M, Hara, K, Tsunoda, M, Murakami, K, Ohteki, T, Uchida, S, Takekawa, S, Waki, H, Tsuno, NH, Shibata, Y, Terauchi, Y, Froguel, P, Tobe, K, Koyasu, S, Taira, K, Kitamura, T, Shimizu, T, Nagai, R, Kadowaki, T	Nature	2003
26578976	Adipokines, diabetes and atherosclerosis: an inflammatory association Freitas Lima, LC, Braga, VA, do Socorro de França Silva, M, Cruz, JC, Sousa Santos, SH, de Oliveira Monteiro, MM, Balarini, CM	Front Physiol	2015