脂聯素
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脂連蛋白(英語:adiponectin,亦稱為脂聯素)是一種主要由脂肪細胞分泌的蛋白質激素,由ADIPOQ基因所編碼[5],含244個氨基酸。成人體內的脂聯素水平與脂肪儲量負相關[來源請求]。
結構
脂聯素包含244個氨基酸,可分為4個結構域。從其N端起算,第一個是使其定位於細胞外的信號序列,第二個區域較短且在物種間高度變異,第三個65個氨基酸的區域與膠原蛋白相似,最後一個是脂聯素的球狀結構域。總的上看,這一蛋白與補體片段C1q相似。其中球狀結構域的三維結構已經測定,結構上與TNFα非常相似,但在氨基酸序列上卻差異巨大[6]。
受體
脂聯素可與幾種受體結合,兩種受體與G蛋白偶聯受體有同源性,一種屬於鈣粘蛋白家族[7][8]:
- 脂聯素受體1 – ADIPOR1
- 脂聯素受體2 – ADIPOR2
- T-cadherin - CDH13
這些受體影響下游靶標AMP激酶,這是一個重要的細胞代謝率控制點。受體的表達與胰島素水平相關,並且在糖尿病小鼠模型中降低,特別是在骨骼肌和脂肪組織中[9][10]。
參考文獻
- ^ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000181092 - Ensembl, May 2017
- ^ 2.0 2.1 2.2 GRCm38: Ensembl release 89: ENSMUSG00000022878 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem. Biophys. Res. Commun. April 1996, 221 (2): 286–9. PMID 8619847. doi:10.1006/bbrc.1996.0587.
- ^ Shapiro L, Scherer PE. The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr. Biol. March 1998, 8 (6): 335–8. PMID 9512423. doi:10.1016/S0960-9822(98)70133-2.
- ^ 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. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423 (6941): 762–9. PMID 12802337. doi:10.1038/nature01705.
- ^ Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc. Natl. Acad. Sci. U.S.A. 2004, 101 (28): 10308–13. PMC 478568 . PMID 15210937. doi:10.1073/pnas.0403382101.
- ^ Fang X, Sweeney G. Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes. Biochem. Soc. Trans. 2006, 34 (Pt 5): 798–801. PMID 17052201. doi:10.1042/BST0340798.
- ^ Bonnard C, Durand A, Vidal H, Rieusset J. Changes in adiponectin, its receptors and AMPK activity in tissues of diet-induced diabetic mice. Diabetes Metab. 2008, 34 (1): 52–61. PMID 18222103. doi:10.1016/j.diabet.2007.09.006.