Overview of the Physiology and Pathophysiology of Leptin With Special Emphasis on its Role in the Kidney

Seminars in Nephrology

Volumn 33, Issue 1, 2013, Pages 54-65

  Nasrallah, Mona P ^a   Ziyadeh, Fuad N ^a  

^a AMERICAN UNIVERSITY OF BEIRUT   (Lebanon)

Author keywords

Hyperleptinemia; Leptin resistance; Obesity; Renal fibrosis

Indexed keywords

ALPHA INTERMEDIN; COLLAGEN TYPE 1; COLLAGEN TYPE 4; LEPTIN; LEPTIN RECEPTOR; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; NEUROPEPTIDE Y; PROOPIOMELANOCORTIN; SODIUM; THYROTROPIN; THYROXINE; TRANSFORMING GROWTH FACTOR BETA1;

APPETITE; ARTICLE; ATHEROSCLEROSIS; CELL FUNCTION; CHRONIC KIDNEY DISEASE; DISEASE ASSOCIATION; ENERGY EXPENDITURE; FATTY LIVER; HUMAN; HYPERLEPTINEMIA; HYPERTENSION; HYPOGONADOTROPIC HYPOGONADISM; HYPOTHYROIDISM; KIDNEY FUNCTION; LEPTIN DEFICIENCY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PATHOGENESIS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; RECEPTOR UPREGULATION; SATIETY; SODIUM RETENTION; TISSUE DISTRIBUTION;

APPETITE REGULATION; ENERGY METABOLISM; HUMANS; KIDNEY; LEPTIN; RECEPTORS, LEPTIN; RENAL INSUFFICIENCY, CHRONIC;

EID: 84873193797     PISSN: 02709295     EISSN: 15584488     Source Type: Journal    
DOI: 10.1016/j.semnephrol.2012.12.005     Document Type: Article

References (85)

1. Ingalls A.M., Dickie M.M., Snell G.D. Obese, a new mutation in the house. J Hered 1950, 37:365-368.
2. Hummel K.P., Dickie M.M., Coleman D.L. Diabetes, a new mutation in the mouse. Science 1966, 153:1127-1128.
3. Coleman D.L. A historical perspective on leptin. Nat Med 2010, 16:1097-1099.
4. Hummel K.P., Coleman D.L., Lane P.W. The Influence of genetic background on expression of mutations at the diabetes locus in the mouse. I. C57BL/KsJ and C57BL/6J strains. Biochem Genet 1972, 7:1-13.
5. Sharma K., McCue P., Dunn S.R. Diabetic kidney disease in the db/db mouse. Am J Physiol Renal Physiol 2003, 284:F1138-F1144.
6. Alpers C.E., Hudkins K.L. Mouse models of diabetic nephropathy. Curr Opin Nephrol Hypertens 2011, 20:278-284.
7. Kumpers P., Gueler F., Rong S., Mengel M., Tossidou I., Peters I., et al. Leptin is a coactivator of TGF-beta in unilateral ureteral obstructive kidney disease. Am J Physiol Renal Physiol 2007, 293:F1355-F1366.
8. Velasquez M., Kimmel P., Michaelis O. Animal models of spontaneous diabetic kidney disease. FASEB J 1990, 4:2850-2859.
9. Mak R.H., Kuo H.J., Cheung W.W. Animal models of obesity-associated chronic kidney disease. Adv Chronic Kidney Dis 2006, 13:374-385.
10. Auwerx J., Staels B. Leptin. Lancet 1998, 351:737-742.
11. Caro J.F., Considine R.V., Kolaczynski J.W., Sinha M.K., Zhang P.L. Leptin: the tale of an obesity gene. Diabetes 1996, 45:1455-1462.
12. Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., Friedman J. Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372:425-432.
13. Margetic S., Gazzola C., Pegg G.G., Hill R.A. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 2002, 26:1407-1433.
14. Winick J.D., Stoffel M., Friedman J.M. Identification of microsatellite markers linked to the human leptin receptor gene on chromosome 1. Genomics 1996, 36:221-222.
15. Wolf G., Chen S., Han D.C., Ziyadeh F.N. Leptin and renal disease. Am J Kidney 2002, 39:1-11.
16. Wolf G., Ziyadeh F. Leptin and renal fibrosis. Obes Kidney 2006, 151:175-183.
17. Tartaglia L.A. The leptin receptor. J Biol Chem 1997, 272:6093-6096.
18. Wauman J., Tavernier J. Leptin receptor signaling: pathways to leptin resistance. Front Biosci 2011, 17:2771-2793.
19. Gorska E., Popko K., Stelmaszczyk-Emmel A., Ciepiela O., Kucharska A., Wasik M. Leptin receptors. Eur J Med Res 2010, 15 Suppl 2:50-54.
20. Murakami T., Yamashita T., Iida M., Kuwajima M., Shima K. A short form of the leptin receptor performs signal transduction. Biochem Biophys Res Commun 1997, 231:26-29.
21. Wolf G., Hamann A., Han D.C., Helmchen U., Thaiss F., Ziyadeh F.N., et al. Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: potential role in glomerulosclerosis. Kidney Int 1999, 56:860-872.
22. Mantzoros C.S., Magkos F., Brinkoetter M., Sienkiewicz E., Dardeno T.A., Kim S.Y., et al. Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab 2011, 301:E567-E584.
23. Bjørbaek C., Uotani S., Da Silva B., Flier J.S. Divergent signaling capacities of the long and short isoforms of the leptin receptor. J Biol Chem 1997, 272:32686-32695.
24. Bjørbaek C., Elmquist J.K., Frantz J.D., Shoelson S.E., Flier J.S. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell 1998, 1:619-625.
25. Yamashita T., Mukarami T., Lida M., Kuwajima M., Shima K. Leptin receptor of Zucker fatty rat performs reduced signal transduction. Diabetes 1997, 46:1077-1080.
26. Chen H., Charlat O., Tartaglia L.A., Woolf E.A., Weng X., Ellis S.J., et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene db/db. Cell 1996, 84:491-495.
27. Rahmouni K., Haynes W.G. Leptin and the cardiovascular system. Recent Prog Horm Res 2004, 59:225-244.
28. Beltowski J. Leptin and the regulation of renal sodium handling and renal Na-transporting ATPases: role in the pathogenesis of arterial hypertension. Curr Cardiol Rev 2010, 6:31-40.
29. Ozcan L., Ergin A.S., Lu A., Chung J., Sarkar S., Nie D., et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab 2009, 9:35-51.
30. Fried S.K., Ricci M.R., Russell C.D., Laferrère B. Regulation of leptin production in humans. J Nutr 2000, 130:3127S-3131S.
31. Borges B.C., Rorato R., Avraham Y., da Silva L., Castro M., Vorobiav L., et al. Leptin resistance and desensitization of hypophagia during prolonged inflammatory challenge. Am J Physiol Endocrinol Metab 2011, 300:E858-E869.
32. Sandoval D.A., Davis S.N. Leptin: metabolic control and regulation. J Diabetes Complications 2003, 17:108-113.
33. Lee M.J., Wang Y., Ricci M.R., Sullivan S., Russell C.D., Fried S.K. Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue. Am J Physiol Endocrinol Metab 2007, 292:E858-E864.
34. Ceccarini G., Flavell R.R., Butelman E.R., Synan M., Willnow T.E., Bar-Dagan M., et al. PET imaging of leptin biodistribution in rodents and primates. Cell Metab 2009, 10:148-159.
35. Sanchez-Lasheras C., Konner C.A., Bruning J.C. Integrative neurobiology of energy homeostasis-neurocircuits, signals and mediators. Front Neuroendocrinol 2010, 31:4-15.
36. Myers M.G. Outstanding Scientific Achievement Award Lecture 2010: deconstructing leptin: from signals to circuits. Diabetes 2010, 59:2708-2714.
37. Leinninger G. Lateral thinking about leptin: a review of leptin action via the lateral hypothalamus. Physiol Behav 2011, 104:572-581.
38. Diéguez C., Vazquez M.J., Romero A., López M., Nogueiras R. Hypothalamic control of lipid metabolism: focus on leptin, ghrelin and melanocortins. Neuroendocrinology 2011, 94:1-11.
39. Buettner C., Muse E.D., Cheng A., Chen L., Scherer T., Pocai A., et al. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat Med 2008, 14:667-675.
40. Li R., Hu Y., Ni Y., Xia D., Grossmann R., Zhao R. Leptin stimulates hepatic activation of thyroid hormones and promotes early posthatch growth in the chicken. Comp Biochem Physiol A Mol Integr Physiol 2011, 160:200-206.
41. Boelen A., Van Beeren M., Vos X., Surovtseva O., Belegri E., Saaltink D.J., et al. Leptin administration restores the fasting-induced increase of hepatic type 3 deiodinase expression in mice. Thyroid 2012, 22:192-199.
42. Elias C.F. Leptin action in pubertal development: recent advances and unanswered questions. Trends Endocrinol Metab 2012, 23:9-15.
43. Denroche H.C., Levi J., Wideman R.D., Sequeira R.M., Huynh F.K., Covey S.D., et al. Leptin therapy reverses hyperglycemia in mice with streptozotocin-induced diabetes, independent of hepatic leptin signaling. Diabetes 2011, 60:1414-1423.
44. Chinookoswong N., Wang J.L., Shi Z.Q. Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat. Diabetes 1999, 48:1487-1492.
45. Ducy P., Amling M., Takeda S., Priemel M., Schilling A.F., Beil F.T., et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Leptin inhibits bone formation through a hypothalamic relay. Cell 2000, 100:197-207.
46. Confavreux C.B. Bone: from a reservoir of minerals to a regulator of energy metabolism. Kidney Int Suppl 2011, 121:S14-S19.
47. Motyl K.J., Rosen C.J. Understanding leptin-dependent regulation of skeletal homeostasis. Biochimie 2012, 94:2089-2096.
48. Hui W., Litherland G.J., Elias M.S., Kitson G.I., Cawston T.E., Rowan A.D., et al. Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases. Ann Rheum Dis 2012, 71:455-462.
49. Sikka G., Yang R., Reid S., Benjo A., Koitabashi N., Camara A., et al. Leptin is essential in maintaining normal vascular compliance independent of body weight. Int J Obesity 2010, 34:203-206.
50. Sweeny G. Cardiovascular effects of leptin. Nat Rev Cardiol 2010, 7:22-29.
51. Petersen K.F., Oral E.A., Dufour S., Befroy D., Ariyan C., Yu C., et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest 2002, 109:1345-1350.
52. Ikejima K., Takei Y., Honda H., Hirose M., Yoshikawa M., Zhang Y.J., et al. Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology 2002, 122:1399-1410.
53. Sahai A., Malladi P., Pan X., Paul R., Melin-Aldana H., Green R.M., et al. Obese and diabetic db/db mice develop marked liver fibrosis in a model of nonalcoholic steatohepatitis: role of short-form leptin receptors and osteopontin. Am J Physiol Gastrointest Liver Physiol 2004, 287:G1035-G1043.
54. Procaccini C., Jirillo E., Matarese G. Leptin as an immunomodulator. Mol Aspects Med 2012, 33:35-45.
55. Hama H., Saito A., Takeda T., Tanuma A., Xie Y., Sato K. Evidence indicating that renal tubular metabolism of leptin is mediated by megalin but not by the leptin receptors. Endocrinology 2004, 145:3935-3940.
56. Widjaja A., Kielstein J.T., Horn R., von zur Mühlen A., Kliem V., Brabant G. Free serum leptin but not bound leptin concentrations are elevated in patients with end-stage renal disease. Nephrol Dial Transplant 2000, 15:846-850.
57. Sharma K., Considine R.V., Michael B., Dunn S.R., Weisberg L.S., Kurnik B.R. Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients. Kidney Int 1997, 51:1980-1985.
58. Dagogo-Jack S., Ovalle F., Landt M., Gearing B., Coyne D.W. Hyperleptinemia in patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis. Perit Dial Int 1998, 18:34-40.
59. Merabet E., Dagogo-Jack S., Coyne D.W., Lein S., Santiago J.V., Hmiel S.P., et al. Increased plasma leptin concentration in end-stage renal disease. J Clin Endocrinol Metab 1997, 82:847-850.
60. Kokot F., Wiecek A., Mesjasz J., Adamczak M., Spiechowicz U. Influence of long-term recombinant human erythropoietin (rHuEpo) therapy on plasma leptin and neuropeptide Y concentration in haemodialysed uraemic patients. Nephol Dial Transplant 1998, 13:1200-1205.
61. Landt M., Brennan D.C., Parvin C.A., Flavin K.S., Dagogo-Jack S., Coyne D.W. Hyperleptinaemia of end-stage renal disease is corrected by renal transplantation. Nephrol Dial Transplant 1998, 13:2271-2275.
62. Briley L.P., Szczech L.A. Leptin and renal disease. Semin Dial 2006, 16:54-59.
63. Mak R.H., Cheung W., Cone R.D., Marks D.L. Leptin and inflammation-associated cachexia in chronic kidney disease. Kidney Int 2006, 69:794-797.
64. Hsu C.Y., McCulloch C.E., Iribarren C., Darbinian J., Go A.S. Body mass index and risk for end-stage renal disease. Ann Intern Med 2006, 144:21-28.
65. Othman M., Kawar B., ElNahas A.M. Influence of obesity on progression of non-diabetic chronic kidney disease: a retrospective cohort study. Nephron Clin Pract 2009, 113:c16-c19.
66. Praga M., Hernandez E., Herrero J.C., Morales E., Revilla Y., Diaz-Gonzalez R., et al. Influence of obesity on the appearance of proteinuria and renal insufficiency after unilateral nephrectomy. Kidney Int 2000, 58:2111-2118.
67. Fenske W.K., Dubb S., Bueter M., Seyfried F., Patel K., Tam F.W., et al. Effect of bariatric surgery-induced weight loss on renal and systemic inflammation and blood pressure: a 12-month prospective study. Surg Obes Relat Dis 2012, In press.
68. Chalmers L., Kaskel F.J., Bangbola O. The role of obesity and its bioclinical correlates in the progression of chronic kidney disease. Adv Chronic Kidney Dis 2006, 13:352-364.
69. Do Carmo J.M., Tallam L.S., Roberts J.V., Brandon J.L., Biglane J., da Silva A.A., et al. Impact of obesity on renal structure and function in the presence and absence of hypertension: evidence from melanocortin-4 receptor-deficient mice. Am J Physiol Regul Integr Comp Physiol 2009, 297:R803-R812.
70. Mark A.L., Shaffer R.A., Correia M.L., Morgan D.A., Sigmund C.D., Haynes W.G. Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice. J Hypertens 1999, 17:1949-1953.
71. Ozata M., Ozdemir I.C., Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab 1999, 84:3686-3695.
72. Galletti F., D'Elia L., Barba G., Siani A., Cappuccio F.P., Farinaro E., et al. High-circulating leptin levels are associated with greater risk of hypertension in men independently of body mass and insulin resistance: results of an eight-year follow-up study. J Clin Endocrinol Metab 2008, 93:3922-3926.
73. Enriori P.J., Sinnayah P., Simonds S.E., Garcia Rudaz C., Cowley M.A. Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown adipose tissue in spite of systemic leptin resistance. J Neurosci 2011, 31:12189-12197.
74. Morgan D.A., Thedens D.R., Weiss R., Rahmouni K. Mechanisms mediating renal sympathetic activation to leptin in obesity. Am J Physiol Regul Integr Comp Physiol 2008, 295:R1730-R1736.
75. Orth S.R., Amann K., Strojek K., Ritz E. Sympathetic overactivity and arterial hypertension in renal failure. Nephrol Dial Transplant 2001, 16:67-69.
76. Wolf G., Helmchen U., Stahl R.A. Isoproterenol stimulates tubular DNA-replication in mice. Nephrol Dial Transplant 1996, 11:2288-2292.
77. Serradeil-Le Gal C., Raufaste D., Brossard G., Pouzet B., Marty E., Maffrand J.P., et al. Characterization and localization of leptin receptors in the rat kidney. FEBS Lett 1997, 404:185-191.
78. Han D.C., Isono M., Chen S., Casaretto A., Hong S.W., Wolf G., et al. Leptin stimulates type I collagen production in db/db mesangial cells: glucose uptake and TGF-beta type II receptor expression. Kidney Int 2001, 59:1315-1323.
79. Suganami T., Mukoyama M., Mori K., Yokoi H., Koshikawa M., Sawai K., et al. Prevention and reversal of renal injury by leptin in a new mouse model of diabetic nephropathy. FASEB J 2005, 19:127-129.
80. Lee M.P., Orlov D., Sweeney G. Leptin induces rat glomerular mesangial cell hypertrophy but does not regulate hyperplasia or apoptosis. Int J Obes 2005, 29:1395-1401.
81. Trujillo J., Cruz C., Tovar A., Vaidya A., Zambrano E., Bonventre J.V., et al. Renoprotective mechanisms of soy protein intake in the obese Zucker rat. Am J Physiol Renal Physiol 2008, 295:F1574-F1582.
82. Babei A., Zarkesh-Esfahani S.H., Bahrami E., Ross R.J. Restricted leptin antagonism as a therapeutic approach to autoimmune diseases. Hormones 2011, 10:16-26.
83. Tumer N., Erdos B., Matheny M., Cudykier I., Scarpace P.J. Leptin antagonist reverses hypertension caused by leptin overexpression, but fails to normalize obesity-related hypertension. J Hypertens 2007, 25:2471-2478.
84. Shpilman M., Niv-Spector L., Katz M., Varol C., Solomon G., Ayalon-Soffer M., et al. Development and characterization of high affinity leptins and leptin antagonists. J Biol Chem 2011, 286:4429-4442.
85. Ziyadeh F.N., Hoffman B.B., Han D.C., Iglesias-de la Cruz M.C., Hong S.W., Isono M., et al. Long-term prevention of renal insufficiency, excess matrix expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice. Proc Natl Acad Sci U S A 2000, 97:8015-8020.