Central leptin gene therapy ameliorates diabetes type 1 and 2 through two independent hypothalamic relays; a benefit beyond weight and appetite regulation

Peptides

Volumn 30, Issue 10, 2009, Pages 1957-1963

  Kalra, Satya P ^a  

^a UNIVERSITY OF FLORIDA   (United States)

Author keywords

Diabetes mellitus type 1 and 2; Hypothalamus; Leptin gene therapy

Indexed keywords

ADENOVIRUS VECTOR; GLUCOSE; INSULIN; LEPTIN; PARVOVIRUS VECTOR;

APPETITE; BODY WEIGHT; DRUG EFFICACY; DRUG SAFETY; ENERGY METABOLISM; GENE THERAPY; GLUCOSE METABOLISM; HORMONE ACTION; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; HYPOTHALAMUS; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RESISTANCE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; PRIMARY PREVENTION; PRIORITY JOURNAL; REVIEW; VIRAL GENE THERAPY;

ANIMALS; APPETITE REGULATION; BODY WEIGHT; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; GLUCOSE; HUMANS; HYPOTHALAMUS; INSULIN; LEPTIN; OBESITY; SIGNAL TRANSDUCTION;

ANIMALIA; PRIMATES; RODENTIA;

EID: 70349316243     PISSN: 01969781     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.peptides.2009.07.021     Document Type: Review

References (93)

1. Bagnasco M., Dube M.G., Kalra P.S., and Kalra S.P. Evidence for the existence of distinct central appetite and energy expenditure pathways and stimulation of ghrelin as revealed by hypothalamic site-specific leptin gene therapy. Endocrinology 143 (2002) 4409-4421
2. Bagnasco M., Dube M.G., Katz A., Kalra P.S., and Kalra S.P. Leptin expression in hypothalamic PVN reverses dietary obesity and hyperinsulinemia but stimulates ghrelin. Obes Res 11 (2003) 1463-1470
3. Banks W.A., DiPalma C.R., and Farrell C.L. Impaired transport of leptin across the blood-brain barrier in obesity. Peptides 20 (1999) 1341-1345
4. Banks W.A., Farr S.A., and Morley J.E. The effects of high fat diets on the blood-brain barrier transport of leptin: failure or adaptation?. Physiol Behav 88 (2006) 244-248
5. Banks W.A., and Farrell C.L. Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible. Am J Physiol Endocrinol Metab 285 (2003) E10-E15
6. Banting F.G., and Best C.H. Pancreatic extracts, 1922. J Lab Clin Med 115 (1990) 254-272
7. Bartness T.J., Kay Song C., Shi H., Bowers R.R., and Foster M.T. Brain-adipose tissue cross talk. Proc Nutr Soc 64 (2005) 53-64
8. Beretta E., Dube M.G., Kalra P.S., and Kalra S.P. Long-term suppression of weight gain, adiposity, and serum insulin by central leptin gene therapy in prepubertal rats: effects on serum ghrelin and appetite-regulating genes. Ped Res 52 (2002) 189-198
9. Boghossian S., Dube M.G., Torto R., Kalra P.S., and Kalra S.P. Hypothalamic clamp on insulin release by leptin-transgene expression. Peptides 27 (2006) 3245-3254
10. Boghossian S., Lecklin A.H., Torto R., Kalra P.S., and Kalra S.P. Suppression of fat deposition for the life time of rodents with gene therapy. Peptides 26 (2005) 1512-1519
11. Boghossian S., Ueno N., Dube M.G., Kalra P., and Kalra S. Leptin gene transfer in the hypothalamus enhances longevity in adult monogenic mutant mice in the absence of circulating leptin. Neurobiol Aging 28 (2007) 1594-1604
12. Bray G.A. Historical framework for the development of ideas about obesity. Handbook of obesity (1998), Marcel Dekker, New York p. 1-29
13. Briley L.P., and Szczech L.A. Leptin and renal disease. Semin Dial 19 (2006) 54-59
14. Buijs R.M., Chun S.J., Niijima A., Romijn H.J., and Nagai K. Parasympathetic and sympathetic control of the pancreas: a role for the suprachiasmatic nucleus and other hypothalamic centers that are involved in the regulation of food intake. J Comp Neurol 431 (2001) 405-423
15. Burguera B., Couce M.E., Curran G.L., Jensen M.D., Lloyd R.V., Cleary M.P., et al. Obesity is associated with a decreased leptin transport across the blood-brain barrier in rats. Diabetes 49 (2000) 1219-1223
16. Caro J.F., Kolaczynski J.W., Nyce M.R., Ohannesian J.P., Opentanova I., Goldman W.H., et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 348 (1996) 159-161
17. Carr M.C., and Brunzell J.D. Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk. J Clin Endocrinol Metab 89 (2004) 2601-2607
18. Carter B.J., and Burstein H. Adeno-associated virus and AAV vectors for gene delivery. In: Templeton-Smith N. (Ed). Theruapeutics mechanisms and strategies (2004), Marcel Dekker, New York NY 71-1011
19. Chinookoswong N., Wang J.L., and Shi Z.Q. Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat. Diabetes 48 (1999) 1487-1492
20. Cohen P., Zhao C., Cai X., Montez J.M., Rohani S.C., Feinstein P., et al. Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest 108 (2001) 1113-1121
21. Correia M.L.G., and Rahmouni K. Role of leptin in the cardiovascular and endocrine complications of metabolic syndrome. Diab Obes Metabol 8 (2006) 603-610
22. Dhillon H., Ge Y., Minter R.M., Prima V., Moldawer L.L., Muzyczka N., et al. Long-term differential modulation of genes encoding orexigenic and anorexigenic peptides by leptin delivered by rAAV vector in ob/ob mice. Relationship with body weight change. Regul Pept 92 (2000) 97-105
23. Dhillon H., Kalra S.P., and Kalra P.S. Dose-dependent effects of central leptin gene therapy on genes that regulate body weight and appetite in the hypothalamus. Mol Ther 4 (2001) 139-145
24. Dhillon H., Kalra S.P., Prima V., Zolotukhin S., Scarpace P.J., Moldawer L.L., et al. Central leptin gene therapy suppresses body weight gain, adiposity and serum insulin without affecting food consumption in normal rats: a long-term study. Regul Pept 99 (2001) 69-77
25. Dube M.G., Beretta E., Dhillon H., Ueno N., Kalra P.S., and Kalra S.P. Central leptin gene therapy blocks high fat diet-induced weight gain, hyperleptinemia and hyperinsulinemia: effects on serum ghrelin levels. Diabetes 51 (2002) 1729-1736
26. Dube M.G., Torto R., and Kalra S.P. Increased leptin expression selectively in the hypothalamus suppresses inflammatory markers CRP and IL-6 in leptin-deficient diabetic obese mice. Peptides 29 (2008) 593-598
27. Dube M.G., Xu B., Kalra P.S., Sninsky C.A., and Kalra S.P. Disruption in neuropeptide Y and leptin signaling in obese ventromedial hypothalamic-lesioned rats. Brain Res 816 (1999) 38-46
28. Ebihara K., Kusakabe T., Hirata M., Masuzaki H., Miyanaga F., Kobayashi N., et al. Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J Clin Endocrinol Metab 92 (2007) 532-541
29. Grundy S.M. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 89 (2004) 2595-2600
30. Hidaka S., Yoshimatsu H., Kondou S., Oka K., Tsuruta Y., Sakino H., et al. Hypoleptinemia, but not hypoinsulinemia, induces hyperphagia in streptozotocin-induced diabetic rats. J Neurochem 77 (2001) 993-1000
31. Hidaka S., Yoshimatsu H., Kondou S., Tsuruta Y., Oka K., Noguchi H., et al. Chronic central leptin infusion restores hyperglycemia independent of food intake and insulin level in streptozotocin-induced diabetic rats. FASEB J 16 (2002) 509-518
32. Iwaniec U.T., Boghossian S., Lapke P.D., Turner R.T., and Kalra S.P. Central leptin gene therapy corrects skeletal abnormalities in leptin-deficient ob/ob mice. Peptides 28 (2007) 1012-1019
33. Kahn S.E., Hull R.L., and Utzschneider K.M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444 (2006) 840-846
34. Kalra P.S., and Kalra S.P. Obesity and metabolic syndrome: long-term benefits of central leptin gene therapy. In: Prous J.R. (Ed). Drugs of today, Barcelona (2002), Prous Science, Spain 745-757
35. Kalra S.P. Central leptin insufficiency syndrome: an interactive etiology for obesity, metabolic and neural diseases and for designing new therapeutic interventions. Peptides 29 (2008) 127-138
36. Kalra S.P. Circumventing leptin resistance for weight control. Proc Natl Acad Sci USA 98 (2001) 4279-4281
37. Kalra S.P. Disruption in the leptin-NPY link underlies the pandemic of diabetes and metabolic syndrome: new therapeutic approaches. Nutrition 24 (2008) 820-826
38. Kalra S.P., Dube M.G., Pu S., Xu B., Horvath T.L., and Kalra P.S. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 20 (1999) 68-100
39. Kalra S.P., and Kalra P.S. Gene transfer technology: a preventive neurotherapy to curb obesity, ameliorate metabolic syndrome and extend life-expectancy. Trends Pharmacol Sci 26 (2005) 488-495
40. Kalra S.P., and Kalra P.S. NPY and cohorts in regulating appetite, obesity and metabolic syndrome: beneficial effects of gene therapy. Neuropeptides 38 (2004) 201-211
41. Kamohara S., Burcelin R., Halaas J.L., Friedman J.M., and Charron M.J. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389 (1997) 374-377
42. Kaplitt M.G., Feigin A., Tang C., Fitzsimons H.L., Mattis P., Lawlor P.A., et al. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. Lancet 369 (2007) 2097-2105
43. Kastin A.J., and Pan W. Dynamic regulation of leptin entry into brain by the blood-brain barrier. Regul Pept 92 (2000) 37-43
44. Kastin A.J., and Pan W. Intranasal leptin: blood-brain barrier bypass (BBBB) for obesity?. Endocrinology 147 (2006) 2086-2087
45. Kastin A.J., Pan W., Maness L.M., Koletsky R.J., and Ernsberger P. Decreased transport of leptin across the blood-brain barrier in rats lacking the short form of the leptin receptor. Peptides 20 (1999) 1449-1453
46. Keen-Rhinehart E., Kalra S.P., and Kalra P.S. AAV mediated leptin receptor installation improves energy balance and the reproductive status of obese female Koletsky rats. Peptides 26 (2005) 2567-2578
47. Kieffer T.J., and Habener J.F. The adipoinsular axis: effects of leptin on pancreatic B-cells. Am J Physiol Endocrinol Metab 278 (2000) E1-E14
48. Kojima S., Akihiro A., Inui A., and Kalra S.P. Leptin as a substitute for insulin therapy in insulin-deficient diabetes-correction of hyperglycemia and hyperphagia and promotion of survival without diabetic complications. 90th Annual Meeting of The Endocrine Society. San Francisco (2008)
49. Kojima S., Asakawa A., Amitani H., Sakoguchi T., Ueno N., Inui A., et al. Central leptin gene therapy, a substitute for insulin therapy to ameliorate hyperglycemia and hyperphagia, and promote survival in insulin-deficient diabetic mice. Peptides 30 (2009) 962-966
50. Koyama K., Shimabukuro M., Chen G., Wang M.Y., Lee Y., Kalra P.S., et al. Resistance to adenovirally induced hyperleptinemia in rats. Comparison of ventromedial hypothalamic lesions and mutated leptin receptors. J Clin Invest 102 (1998) 728-733
51. Kreier F., Kap Y.S., Mettenleiter T.C., van Heijningen C., van der Vliet J., Kalsbeek A., et al. Tracing from fat tissue, liver, and pancreas: a neuroanatomical framework for the role of the brain in type 2 diabetes. Endocrinology 147 (2006) 1140-1147
52. Kurrimbux D., Gaffen Z., Farrell C.L., Martin D., and Thomas S.A. The involvement of the blood-brain and the blood-cerebrospinal fluid barriers in the distribution of leptin into and out of the rat brain. Neuroscience 123 (2004) 527-536
53. Lazar M.A. How obesity causes diabetes: not a tall tale. Science 307 (2005) 373-375
54. Lecklin A.H., Dube M.G., Torto R., Kalra P.S., and Kalra S.P. Perigestational suppression of weight gain with central leptin gene therapy results in lower weight F1 generation. Peptides 26 (2005) 1176-1187
55. Lewis G.F., Carpentier A., Adeli K., and Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 23 (2002) 201-229
56. Lin C.Y., Higginbotham D.A., Judd R.L., and White B.D. Central leptin increases insulin sensitivity in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab 282 (2002) E1084-E1091
57. Lin E.J., Sainsbury A., Lee N.J., Boey D., Couzens M., Enriquez R., et al. Combined deletion of Y1, Y2, and Y4 receptors prevents hypothalamic neuropeptide Y overexpression-induced hyperinsulinemia despite persistence of hyperphagia and obesity. Endocrinology 147 (2006) 5094-5101
58. Lord G. Role of leptin in immunology. Nutr Rev 60 (2002) S35-S38 S68-87
59. Luchsinger J.A., Reitz C., Patel B., Tang M.X., Manly J.J., and Mayeux R. Relation of diabetes to mild cognitive impairment. Arch Neurol 64 (2007) 570-575
60. Malhotra A., Vashistha H., Yadav V.S., Dube M.G., Kalra S.P., Abdellatif M., et al. Inhibition of p66ShcA redox activity in cardiac muscle cells attenuates hyperglycemia-induced oxidative stress and apoptosis. Am J Physiol Heart Circ Physiol 296 (2009) H380-H388
61. Minokoshi Y., Haque M.S., and Shimazu T. Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats. Diabetes 48 (1999) 287-291
62. Miyanaga F., Ogawa Y., Ebihara K., Hidaka S., Tanaka T., Hayashi S., et al. Leptin as an adjunct of insulin therapy in insulin-deficient diabetes. Diabetologia 46 (2003) 1329-1337
63. Moller D.E. New drug targets for type 2 diabetes and the metabolic syndrome. Nature 414 (2001) 821-827
64. Murphy J.E., Zhou S., Giese K., Williams L.T., Escobedo J.A., and Dwarki V.J. Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin. Proc Natl Acad Sci USA 94 (1997) 13921-13926
65. Muzzin P., Eisensmith R.C., Copeland K.C., and Woo S.L. Correction of obesity and diabetes in genetically obese mice by leptin gene therapy. Proc Natl Acad Sci USA 93 (1996) 14804-14808
66. Ogawa Y., Masuzaki H., Hosoda K., Aizawa-Abe M., Suga J., Suda M., et al. Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin. Diabetes 48 (1999) 1822-1829
67. Olshansky S.J., Passaro D.J., Hershow R.C., Layden J., Carnes B.A., Brody J., et al. A potential decline in life expectancy in the United States in the 21st century. N Engl J Med 352 (2005) 1138-1145
68. O'Rahilly S., Farooqi I.S., Yeo G.S., and Challis B.G. Minireview: human obesity-lessons from monogenic disorders. Endocrinology 144 (2003) 3757-3764
69. Oral E.A., Simha V., Ruiz E., Andewelt A., Premkumar A., Snell P., et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med 346 (2002) 570-578
70. Otukonyong E.E., Dube M.G., Torto R., Kalra P.S., and Kalra S.P. Central leptin differentially modulates ultradian secretory patterns of insulin, leptin and ghrelin independent of effects on food intake and body weight. Peptides 26 (2005) 2559-2566
71. Otukonyong E.E., Dube M.G., Torto R., Kalra P.S., and Kalra S.P. High fat diet-induced ultradian leptin and insulin hypersecretion and ghrelin is absent in obesity-resistant rats. Obes Res I13 (2005) 991-999
72. Owens D.R., Zinman B., and Bolli G.B. Insulins today and beyond. Lancet 358 (2001) 739-746
73. Pan W., and Kastin A.J. Why study transport of peptides and proteins at the neurovascular interface. Brain Res Brain Res Rev 46 (2004) 32-43
74. 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 109 (2002) 1345-1350
75. Pu S, Dube MG, Kalra SP, Kalra PS. Permanent interruption of information flow between hypothalamus and hindbrain produces obesity accompanied by a selective dark-phase hyperphagia and hyperinsulinemia. New Orleans, LA, 2003, W-33, Abs #831.7.
76. Shi Z.Q., Nelson A., Whitcomb L., Wang J., and Cohen A.M. Intracerebroventricular administration of leptin markedly enhances insulin sensitivity and systemic glucose utilization in conscious rats. Metabolism 47 (1998) 1274-1280
77. Shimomura I., Hammer R.E., Ikemoto S., Brown M.S., and Goldstein J.L. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401 (1999) 73-76
78. Sierra-Honigmann M.R., Nath A.K., Murakami C., Garcia-Cardena G., Papapetropoulos A., Sessa W.C., et al. Biological action of leptin as an angiogenic factor. Science 281 (1998) 1683-1686
79. Slyper A.H. The pediatric obesity epidemic: causes and controversies. J Clin Endocrinol Metab 89 (2004) 2540-2547
80. Stein C.J., and Colditz G.A. The epidemic of obesity. J Clin Endocrinol Metab 89 (2004) 2522-2525
81. Szanto I., and Kahn C.R. Selective interaction between leptin and insulin signaling pathways in a hepatic cell line. Proc Natl Acad Sci USA 97 (2000) 2355-2360
82. Taubes G. Diabetes. Paradoxical effects of tightly controlled blood sugar. Science 322 (2008) 365-367
83. Ueno N., Dube M.G., Inui A., Kalra P.S., and Kalra S.P. Leptin modulates orexigenic effects of ghrelin and attenuates adiponectin and insulin levels and selectively the dark-phase feeding as revealed by central leptin gene therapy. Endocrinology 145 (2004) 4176-4184
84. Ueno N., Inui A., Kalra S.P., and Kalra P.S. Leptin transgene expression in the hypothalamus enforces euglycemia in diabetic, insulin-deficient nonobese Akita mice and leptin-deficient obese ob/ob mice. Peptides 27 (2006) 2332-2342
85. Unger R.H. Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine. Biochimie 87 (2005) 57-64
86. Uyama N., Geerts A., and Reynaert H. Neural connections between the hypothalamus and the liver. Anat Rec A Discov Mol Cell Evol Biol 280 (2004) 808-820
87. Van Heek M., Compton D.S., France C.F., Tedesco R.P., Fawzi A.B., Graziano M.P., et al. Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J Clin Invest 99 (1997) 385-390
88. Wang J., Takeuchi T., Tanaka S., Kubo S.K., Kayo T., Lu D., et al. A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouse. J Clin Invest 103 (1999) 27-37
89. Wang J.L., Chinookoswong N., Scully S., Qi M., and Shi Z.Q. Differential effects of leptin in regulation of tissue glucose utilization in vivo. Endocrinology 140 (1999) 2117-2124
90. Wang Z.W., Zhou Y.T., Kakuma T., Lee Y., Higa M., Kalra S.P., et al. Comparing the hypothalamic and extrahypothalamic actions of endogenous hyperleptinemia. Proc Natl Acad Sci USA 96 (1999) 10373-10378
91. Yoshioka M., Kayo T., Ikeda T., and Koizumi A. A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice. Diabetes 46 (1997) 887-894
92. Yu X., Park B.H., Wang M.Y., Wang Z.V., and Unger R.H. Making insulin-deficient type 1 diabetic rodents thrive without insulin. Proc Natl Acad Sci USA 105 (2008) 14070-14075
93. Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., and Friedman J.M. Positional cloning of the mouse obese gene and its human homologue. Nature 372 (1994) 425-432