生化学事典
脂肪細胞から特異的に分泌されるコラーゲン様タンパク質。アディポサイトカインの中で最も血中濃度が高い（5-10g/mL)
224アミノ酸で構成され、血中では三量体を形成し、六量体が活性型である。肥満に伴い血中濃度の低下が見られる。
動脈硬化に対し抑制的な作用を持つ。
ヴォート基礎生化学4th
アディポネクチンは247残基のペプチドホルモンで、AMPK活性を調節することでエネルギーホメオスタシス、グルコース代謝脂質代謝の調節を助ける。
単量体はN末端のコラーゲン用ドメインが三本螺旋を巻いて生成する三量体である。これがジスルフィド架橋し六量体の中分子量型、更に多量体をつくる高分子量型も形成される。
アディポネクチン受容体が肝臓、骨格筋にあり、刺激によりAMPKのリン酸化が進み活性化する。（肝臓で糖新生抑制、脂肪酸酸化促進、骨格筋でグルコースの取り込み、酸化脂肪酸の酸化が進む）これらはインスリンに帯する応答と同じで、インスリンに対する感度を上げるため、アディポネクチンの活性が低下することでインスリン抵抗性が発現すると考えられる。
脂肪細胞が増加するとアディポネクチン濃度が低下するが、TNFαの産生増加と関係があると考えられている。
UNIPROT
http://www.uniprot.org/uniprot/Q15848
Adiponectin
GeneADIPOQ
Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver and macrophages, and also by counteracting its effects. Inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway. May play a role in cell growth, angiogenesis and tissue remodeling by binding and sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW.
Post-translational modificationi
Hydroxylated Lys-33 was not identified in PubMed:16497731, probably due to poor representation of the N-terminal peptide in mass fingerprinting.1 Publication
HMW complexes are more extensively glycosylated than smaller oligomers. Hydroxylation and glycosylation of the lysine residues within the collagene-like domain of adiponectin seem to be critically involved in regulating the formation and/or secretion of HMW complexes and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes (By similarity).By similarity
O-glycosylated. Not N-glycosylated. O-linked glycans on hydroxylysines consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups. Sialylated to varying degrees depending on tissue. Thr-22 appears to be the major site of sialylation. Higher sialylation found in SGBS adipocytes than in HEK fibroblasts. Sialylation is not required neither for heterodimerization nor for secretion. Not sialylated on the glycosylated hydroxylysines. Desialylated forms are rapidly cleared from the circulation.
Subunit structurei
Homomultimer. Forms trimers, hexamers and 12- to 18-mers. The trimers (low molecular weight complexes / LMW) are assembled via non-covalent interactions of the collagen-like domains in a triple helix and hydrophobic interactions within the globular C1q domain. Several trimers can associate to form disulfide-linked hexamers (middle molecular weight complexes / MMW) and larger complexes (higher molecular weight / HMW). The HMW-complex assembly may rely additionally on lysine hydroxylation and glycosylation. LMW, MMW and HMW complexes bind to HBEGF, MMW and HMW complexes bind to PDGFB, and HMW complex binds to FGF2. Interacts with CTRP9A via the C1q domain (heterotrimeric complex) (By similarity).
Adiponectin receptors: a review of their structure, function and how they work.(PMID:24417942)
http://europepmc.org/abstract/MED/24417942
Adiponectin exerts its effects by binding to adiponectin receptors, two of which, AdipoR1 and AdipoR2, have been cloned. This has enabled researchers to carry out detailed studies elucidating the role played by these receptors and the metabolic pathways that are involved following their activation. Such studies have clearly shown that the stimulation of these receptors is associated with glucose homeostasis and ongoing research into their role will clarify the underlying molecular mechanisms of adiponectin. Such knowledge can then be used to provide therapeutic targets aimed at managing obesity-linked diseases including type 2 diabetes and metabolic syndrome.
