Mechanisms Linking Obesity, Chronic Kidney Disease, and Fatty Liver Disease: the Roles of Fetuin-A, Adiponectin, and AMPK

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2010 Feb 13

PMID 20150538

Citations 137

Authors

Joachim H Ix

Kumar Sharma

Affiliations

Soon will be listed here.

Abstract

Obesity is a risk factor for chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD). Recent studies identify mechanisms common to both diseases linked through an interorgan communication orchestrated by fetuin-A and adiponectin. In liver and kidney, the energy sensor 5'-AMP activated protein kinase (AMPK) is pivotal to directing podocytes and hepatocytes to compensatory and potentially deleterious pathways, leading to inflammatory and profibrotic cascades culminating in end-organ damage. Regulation of these early upstream pathways may provide new therapeutic targets for these increasingly common sequelae of obesity.

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References

Menon V, Li L, Wang X, Greene T, Balakrishnan V, Madero M . Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol. 2006; 17(9):2599-606. DOI: 10.1681/ASN.2006040331. View

Wolf G, Ziyadeh F . Leptin and renal fibrosis. Contrib Nephrol. 2006; 151:175-183. DOI: 10.1159/000095328. View

Stefan N, Hennige A, Staiger H, Machann J, Schick F, Krober S . Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care. 2006; 29(4):853-7. DOI: 10.2337/diacare.29.04.06.dc05-1938. View

Ohashi N, Kato A, Misaki T, Sakakima M, Fujigaki Y, Yamamoto T . Association of serum adiponectin levels with all-cause mortality in hemodialysis patients. Intern Med. 2008; 47(6):485-91. DOI: 10.2169/internalmedicine.47.0614. View

Laughlin G, Barrett-Connor E, May S, Langenberg C . Association of adiponectin with coronary heart disease and mortality: the Rancho Bernardo study. Am J Epidemiol. 2006; 165(2):164-74. PMC: 2642645. DOI: 10.1093/aje/kwk001. View

Reinehr T, Kiess W, de Sousa G, Stoffel-Wagner B, Wunsch R . Intima media thickness in childhood obesity: relations to inflammatory marker, glucose metabolism, and blood pressure. Metabolism. 2005; 55(1):113-8. DOI: 10.1016/j.metabol.2005.07.016. View

Looker H, Krakoff J, Funahashi T, Matsuzawa Y, Tanaka S, Nelson R . Adiponectin concentrations are influenced by renal function and diabetes duration in Pima Indians with type 2 diabetes. J Clin Endocrinol Metab. 2004; 89(8):4010-7. DOI: 10.1210/jc.2003-031916. View

Kadowaki T, Yamauchi T, Kubota N . The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Lett. 2007; 582(1):74-80. DOI: 10.1016/j.febslet.2007.11.070. View

Kataoka H, Sharma K . Renal handling of adipokines. Contrib Nephrol. 2006; 151:91-105. DOI: 10.1159/000095321. View

10.

Mokdad A, Ford E, Bowman B, Dietz W, Vinicor F, Bales V . Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2002; 289(1):76-9. DOI: 10.1001/jama.289.1.76. View

11.

Xie Z, Dong Y, Scholz R, Neumann D, Zou M . Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells. Circulation. 2008; 117(7):952-62. PMC: 2862466. DOI: 10.1161/CIRCULATIONAHA.107.744490. View

12.

Collins S, Peacock W, Lindsell C, Clopton P, Diercks D, Hiestand B . S3 detection as a diagnostic and prognostic aid in emergency department patients with acute dyspnea. Ann Emerg Med. 2009; 53(6):748-57. DOI: 10.1016/j.annemergmed.2008.12.029. View

13.

Yano Y, Hoshide S, Ishikawa J, Hashimoto T, Eguchi K, Shimada K . Differential impacts of adiponectin on low-grade albuminuria between obese and nonobese persons without diabetes. J Clin Hypertens (Greenwich). 2007; 9(10):775-82. PMC: 8110132. DOI: 10.1111/j.1524-6175.2007.07321.x. View

14.

Persson F, Rossing P, Hovind P, Stehouwer C, Schalkwijk C, Tarnow L . Endothelial dysfunction and inflammation predict development of diabetic nephropathy in the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA 2) study. Scand J Clin Lab Invest. 2008; 68(8):731-8. DOI: 10.1080/00365510802187226. View

15.

Flegal K, Carroll M, Ogden C, Johnson C . Prevalence and trends in obesity among US adults, 1999-2000. JAMA. 2002; 288(14):1723-7. DOI: 10.1001/jama.288.14.1723. View

16.

Kasinath B, Mariappan M, Sataranatarajan K, Lee M, Feliers D . mRNA translation: unexplored territory in renal science. J Am Soc Nephrol. 2006; 17(12):3281-92. DOI: 10.1681/ASN.2006050488. View

17.

Ran J, Hirano T, Fukui T, Saito K, Kageyama H, Okada K . Angiotensin II infusion decreases plasma adiponectin level via its type 1 receptor in rats: an implication for hypertension-related insulin resistance. Metabolism. 2006; 55(4):478-88. DOI: 10.1016/j.metabol.2005.10.009. View

18.

Davis B, Xie Z, Viollet B, Zou M . Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes. 2006; 55(2):496-505. DOI: 10.2337/diabetes.55.02.06.db05-1064. View

19.

Stefan N, Fritsche A, Weikert C, Boeing H, Joost H, Haring H . Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes. 2008; 57(10):2762-7. PMC: 2551687. DOI: 10.2337/db08-0538. View

20.

Hui J, Hodge A, Farrell G, Kench J, Kriketos A, George J . Beyond insulin resistance in NASH: TNF-alpha or adiponectin?. Hepatology. 2004; 40(1):46-54. DOI: 10.1002/hep.20280. View