Кобыляк Н.М., Михальчишин Г.П., Савченюк А.А., Фалалеева Т.М.

ПАТОФИЗИОЛОГИЧЕСКАЯ РОЛЬ АДИПОНЕКТИНА В РАЗВИТИИ ОЖИРЕНИЯ И СОПУТСТВУЮЩИХ ЗАБОЛЕВАНИЙ

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Об авторе:	Кобыляк Н.М., Михальчишин Г.П., Савченюк А.А., Фалалеева Т.М.
Рубрика	ОБЗОРЫ ЛИТЕРАТУРЫ
Тип статьи	Обзорная статья
Аннотация	Приведенный анализ научных статей, посвященных механизмам действия адипонектина, его роли в метаболизме и в патогенезе заболеваний. Показано снижение содержания глюкозы, триглицеридов, липопротеидов низкой плотности в крови под действием адипонектина. Пониженная концентрация в крови адипонектина была отмечена при ожирении, инсулинорезистентности, неалкогольном стеатогепатите, атеросклерозе и дисфункции эндотелия. Таким образом, учитывая спектр действия адипонектина, активация внутриклеточных каскадов, опосредованных этим гормоном, создает поле исследований для поиска и внедрения эффективных терапевтических средств для лечения указанных заболеваний.
Ключевые слова	адипонектин, метаболизм, ожирение, инсулинорезистентность, неалкогольный стеатогепатит, атеросклероз
Список цитируемой литературы	Arita Y.  Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell / Y. Arita, S. Kihara, N. Ouchi [et al.]   // Circulation - 2002, Vol. 105: P.2893–2898. Berg  A. H. ACRP30/ adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol. Metab / A.H. Berg, T.P. Combs & T.P. Scherer // - 2002, Vol. 13,  P.84–89. Bobbert T. Changes of adiponectin oligomer composition by moderate weight reduction / T. Bobbert [et al.]  // - 2005, Diabetes 54, P. 2712–2719. Combs T.P. A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity. Endocrinology / T.P. Combs, U.B. Pajvani, A.H. Berg [et al.]  //- 2004,Vol. 145: P.367–383. Ebinuma H. Improved ELISA for selective measurement of adiponectin multimers and identification of adiponectin in human cerebrospinal fluid. Clin Chem / H. Ebinuma, T. Miida, T. Yamauchi, [et al.]  // -2007,Vol. 53(8): P. 1541-1544. Gu H.F. Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetes in Swedish caucasians. Diabetes / H.F. Gu, A. Abulaiti, C.G. Ostenson [et al.]  // - 2004; Vol.53, P.31–35. Hu E. AdipoQ is a novel adipose-specific gene dysregulated in obesity / E. Hu, P. Liang, B.M. Spiegelman [et al.]  // - J Biol Chem -1996; Vol 271: P. 10697–10703. Hotta K. Circulating Concentrations of the Adipocyte Protein Adiponectin Are Decreased in Parallel With Reduced Insulin Sensitivity During the Progression to Type 2 Diabetes in Rhesus Monkeys. Diabetes / K. Hotta, T. Funahashi, N.L. Bodkin [et al.] // - 2001; Vol. 50, P.1126–1133. Hara K. Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes / K. Hara, P. Boutin, Y. Mori [et al.] // - 2002, Vol.51: P.536–540. Hui J.M. Beyond insulin resistance in NASH. TNF-alpha or adiponectin? Hepatology / J.M. Hui, A. Hodge, G.C. Farrell [et al.]  // -  2004, Vol.40: P.46–54. Hug C.  T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin / C. Hug, J. Wang, N.S. Ahmad [et al.]    //  Proc Natl Acad Sci U S A, - 2004, Vol.101(28): P. 10308-10313. Kubota N. Disruption adiponectin causes insulin resistance neointimal formation. J Biol Chem / N. Kubota, Y. Terauchi, T Yamauchi [et al.]  //- 2002, Vol. 277,  P. 25863–25866. Kamada Y. Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin. Gastroenterology / Y.  Kamada [et al.]  // - 2003, Vol.125: P. 1796–1807. Kobayashi H.   Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin / H. Kobayashi, N. Ouchi, S. Kihara [et al.]  // Circ Res - 2004,Vol. 94(4): P.27-31. Kaser S. Adiponectin and its receptors in non-alcoholic steatohepatitis / S. Kaser, A. Moschen, A. Cayon [et al.]  // Gut - 2005, Vol.54, P. 117–121. Kadowaki T.  Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome / T. Kadowaki, T. Yamauchi, N. Kubota [et al.]   // J Clin Invest - 2006, Vol. 116(7):P. 1784-92. Kubota N. Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab / N. Kubota, W. Yano, T. Kubota [et al.] //  - 2007, Vol. 6(1): P. 55-68. Lopez-Bermejo A. Adiponectin, hepatocellular dysfunction and insulin sensitivity. Clin Endocrinol Oxf / A. Lopez-Bermejo [et al.]  //-2004, Vol. 60, P. 256–263. Maeda K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). / K. Maeda, K. Okubo, I. Shimomura [et al.] //  Biochem Biophys Res Commun 1996, Vol. 221: P. 286–289. Maeda N. PPARγ ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein / N.  Maeda [et al.]  // Diabetes 50,-2001, P. 2094–2099. Maeda N. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 / N. Maeda, I. Shimomura, K. Kishida [et al.]  //-  Nat Med - 2002, Vol.8, P.731–737. Masaki T.  Adiponectin protects LPSinduced liver injury through modulation of TNF-α in KK-Ay obese mice / T. Masaki [et al.] //  Hepatology- 2004,  Vol. 40: P.177–184. Nakano Y. Isolation and characterization of GBP28, a novel gelatinbinding protein purified from human plasma / Y. Nakano, T. Tobe, N.H. Choi-Miura [et al.]   //- J Biochem (Tokyo) -1996, Vol. 120, P.803–812. Ng T.W. Adipocytokines and VLDL metabolism: independent regulatory effects of adiponectin, insulin resistance, and fat compartments on VLDL apolipoprotein B-100 kinetics? Diabetes / T.W. Ng [et al.] //-2005, Vol. 54, P. 795–802. Nawrocki A.R. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor-γ agonists / A.R. Nawrocki [et al.]  //- J. Biol. Chem - 2006, Vol.281, P.2654–2660. Ouchi N. Novel modulator for endothelial adhesion molecules: adipocytederived plasma protein adiponectin. Circulation / N. Ouchi, S. Kihara, Y. Arita [et al.]  //-1999, Vol. 100, P.2473–2476. Ouchi  N. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages / N. Ouchi, S. Kihara, Y. Arita [et al.]   // Circulation - 2001, Vol.103(8): P. 1057-1063. Okamoto Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation / Y.Okamoto, S. Kihara, N. Ouchi [et al.]  //- 2002; Vol. 10, P. 2767–2770. Ouchi N.  Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol / N.Ouchi, S. Kihara, T. Funahashi [et al.]  // - 2003; Vol.14: P.561–566. Pajvani U.B. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity / U.B.  Pajvani, X. Du, T.P. Combs [et al.]   //J Biol Chem, - 2003, Vol. 278(11):P. 9073-9085 Pajvani U.B. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity / Pajvani, U. B. [et al.]  // J. Biol. Chem.- 2004, Vol. 279, P. 12152–12162. Resink T.J. LDL binds to surface-expressed human T-cadherin in transfected HEK293 cells and influences homophilic adhesive interactions / T.J. Resink, Y.S. Kuzmenko, F. Kern [et al.] // FEBS Lett,-1999,Vol.  463(1-2): P. 29-34. Scherer P.E. A novel serum protein similar to C1q, produced exclusively in adipocytes / P.E. Scherer, S. Williams, M. Fogliano, [et al.] // J Biol Chem - 1995, Vol. 270, P. 26746–26749. Shklyaev S. [et al.] (2003) Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats / Shklyaev S. [et al.]  // - 2003,  Proc Natl Acad Sci U S A Vol. 100: P.14217–14222. Shimada K.  Adiponectin and atherosclerotic disease / K. Shimada, T. Miyazaki, H. Daida // Clin Chim Acta - 2004,Vol 344(1-2)P.1-12. Tilg H. Adipocytokines: mediators linking adipose tissue, inflammation and immunity / H. Tilg, A.R. Moschen // Nat Rev Immunol - 2006, Vol. 6(10): P.772-783. Targher G. Decreased plasma adiponectin concentrations are closely associated with nonalcoholic hepatic steatosis in obese individuals / G. Targher, L. Bertolini, L. Scala [et al.]  // -2004; Vol.61: P.700–703. Tsuchida A. Insulin/foxo1 pathway regulates expression levels adiponectin receptors adiponectin sensitivity. J Biol Chem / A.Tsuchida, T.Yamauchi, Y. Ito [et al.]  // - 2004, Vol.279: P. 30817–30822. Vasseur F. Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocytesecreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet / F.Vasseur, N. Helbecque, C. Dina [et al.] // -  2002, Vol.11: P.2607–2614. Vuppalanchi R. Is adiponectin involved in the pathogenesis of nonalcoholic steatohepatitis? A preliminary human study. J Clin Gastroenterol / R. Vuppalanchi [et al.]  //- 2005, Vol. 39, P. 237–242. Wolf A.M.   Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem. Biophys. Res. Commun / A.M.Wolf, D.Wolf, H.Rumpold [et al.] // - 2004, Vol. 323, P. 630–635. Waki H. Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1/ H. Waki, T. Yamauchi, J. Kamon  [et al.]   // Endocrinology - 2005, Vol. 146(2): P. 790-796. Wan Y. Post-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex / Y.Wang, K.S. Lam, L. Chan [et al.]  // J Biol Chem,2006, Vol. 281(24): P. 16391-16400. Whitehead J.P. [et al.] Adiponectin - a key adipokine in the metabolic syndrome. Diabetes Obes Metab / J.P.  Whitehead [et al.]  //- 2006,  Vol. 8(3), P.264-280. Xu A. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty  liver diseases in mice. J Clin Invest / A. Xu, Y. Wang, H. Keshaw [et al.]  // - 2003, Vol. 112: P. 91–100. Yokota T.  Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages / T. Yokota [et al.]  //-  Blood 96 - 2000, P.1723–1732. Yamauchi T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMPactivated protein kinase. Nature Med / T. Yamauchi [et al.]  //-2002, Vol. 8, P.1288–1295. Yamauchi T. [et al.] Cloning of adiponectin receptors that mediate antidiabetic metabolic effects / T. Yamauchi [et al.] //- 2003, Nature 423, P. 762–769. Yamaguchi N.  Adiponectin inhibits Toll-like receptor family-induced signaling / N. Yamaguchi [et al.]  // FEBS Lett - 2005, Vol.579, P. 6821–6826. Yoon Y.S. Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis. Exp Mol Med / Y.S.Yoon, D. Ryu, M.W. Lee [et al.]  // - 2009.
Публикация статьи	«Мир Медицины и Биологии» №3(40) 2 часть 2013 год, 081-087 страницы, код УДК 616.1/3-02:[577.17:611-018.26]