Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity

Journal of Neuroscience

Volumn 30, Issue 48, 2010, Pages 16180-16187

  Koch, Christiane ^a   Augustine, Rachael A ^b   Steger, Juliane ^a   Ganjam, Goutham K ^a   Benzler, Jonas ^a   Pracht, Corinna ^a   Lowe, Chrishanthi ^a   Schwartz, Michael W ^d   Shepherd, Peter R ^c   Anderson, Greg M ^b   Grattan, David R ^b   Tups, Alexander ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b UNIVERSITY OF OTAGO   (New Zealand)

^c UNIVERSITY OF AUCKLAND   (New Zealand)

^d UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; INSULIN; INSULIN RECEPTOR SUBSTRATE 1; LEPTIN; LEPTIN RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY FAT; BODY MASS; CONTROLLED STUDY; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; HYPERGLYCEMIA; HYPOTHALAMUS; INSULIN SENSITIVITY; MALE; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; RAT;

ADIPOSE TISSUE; ANIMALS; BLOOD GLUCOSE; CLASS IA PHOSPHATIDYLINOSITOL 3-KINASE; CLASS IB PHOSPHATIDYLINOSITOL 3-KINASE; GLUCOSE; HOMEOSTASIS; HYPOTHALAMUS; INSULIN RESISTANCE; ISOENZYMES; LEPTIN; MALE; MICE; MICE, KNOCKOUT; MICE, OBESE; OBESITY; RATS; RATS, SPRAGUE-DAWLEY; TIME FACTORS;

EID: 78649753017     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.3202-10.2010     Document Type: Article

References (38)

1. Brüning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Müller-Wieland D, Kahn CR (2000) Role of brain insulin receptor in control of body weight and reproduction. Science 289:2122-2125.
2. Choudhury AI, Heffron H, Smith MA, Al-Qassab H, Xu AW, Selman C, Simmgen M, Clements M, Claret M, Maccoll G, Bedford DC, Hisadome K, Diakonov I, Moosajee V, Bell JD, Speakman JR, Batterham RL, Barsh GS, Ashford ML, Withers DJ (2005) The role of insulin receptor substrate 2 in hypothalamic and beta cell function. J Clin Invest 115:940-950.
3. Copps KD, Hancer NJ, Opare-Ado L, Qiu W, Walsh C, White MF (2010) Irs1 serine 307 promotes insulin sensitivity in mice. Cell Metab 11:84-92.
4. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O'Rahilly S (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341:879-884.
5. Folli F, Bonfanti L, Renard E, Kahn CR, Merighi A (1994) Insulin receptor substrate-1 (IRS-1) distribution in the rat central nervous system. J Neurosci 14:6412-6422.
6. Fukuda M, Jones JE, Olson D, Hill J, Lee CE, Gautron L, Choi M, Zigman JM, Lowell BB, Elmquist JK (2008) Monitoring FoxO1 localization in chemically identified neurons. J Neurosci 28:13640-13648.
7. Gelling RW, Morton GJ, Morrison CD, Niswender KD, Myers MG Jr, Rhodes CJ, Schwartz MW (2006) Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes. Cell Metab 3:67-73.
8. German J, Kim F, Schwartz GJ, Havel PJ, Rhodes CJ, Schwartz MW, Morton GJ (2009) Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a neurocircuit involving the vagus nerve. Endocrinology 150:4502-4511.
9. German JP, Wisse BE, Thaler JP, Oh-IS, Sarruf DA, Ogimoto K, Kaiyala KJ, Fischer JD, Matsen ME, Taborsky GJ Jr, Schwartz MW, Morton GJ (2010) Leptin deficiency causes insulin resistance induced by uncontrolled diabetes. Diabetes 59:1626-1634.
10. Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, Rebholz H, Barnett J, Leslie NR, Cheng S, Shepherd PR, Gout I, Downes CP, Lamb RF (2004) The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol 166:213-223.
11. Hedbacker K, Birsoy K, Wysocki RW, Asilmaz E, Ahima RS, Farooqi IS, Friedman JM (2010) Antidiabetic effects of IGFBP2, a leptin-regulated gene. Cell Metab 11:11-22.
12. Hill JW, Williams KW, Ye C, Luo J, Balthasar N, Coppari R, Cowley MA, Cantley LC, Lowell BB, Elmquist JK (2008) Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice. J Clin Invest 118:1796-1805.
13. Hill JW, Xu Y, Preitner F, Fukuda M, Cho YR, Luo J, Balthasar N, Coppari R, Cantley LC, Kahn BB, Zhao JJ, Elmquist JK (2009) Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis. Endocrinology 150:4874-4882.
14. Kievit P, Howard JK, Badman MK, Balthasar N, Coppari R, Mori H, Lee CE, Elmquist JK, Yoshimura A, Flier JS (2006) Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells. Cell Metab 4:123-132.
15. Koch L, Wunderlich FT, Seibler J, Könner AC, Hampel B, Irlenbusch S, Brabant G, Kahn CR, Schwenk F, Brüning JC (2008) Central insulin action regulates peripheral glucose and fat metabolism in mice. J Clin Invest 118:2132-2147.
16. Kubota N, Terauchi Y, Tobe K, Yano W, Suzuki R, Ueki K, Takamoto I, Satoh H, Maki T, Kubota T, Moroi M, Okada-Iwabu M, Ezaki O, Nagai R, Ueta Y, Kadowaki T, Noda T (2004) Insulin receptor substrate 2 plays a crucial role in beta cells and the hypothalamus. J Clin Invest 114:917-927.
17. Lin X, Taguchi A, Park S, Kushner JA, Li F, Li Y, White MF (2004) Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes. J Clin Invest 114:908-916.
18. Mauvais-Jarvis F, Ueki K, Fruman DA, Hirshman MF, Sakamoto K, Goodyear LJ, Iannacone M, Accili D, Cantley LC, Kahn CR (2002) Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. J Clin Invest 109:141-149.
19. Morton GJ, Gelling RW, Niswender KD, Morrison CD, Rhodes CJ, Schwartz MW (2005) Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab 2:411-420.
20. Muzzin P, Eisensmith RC, Copeland KC, Woo SL (1996) Correction of obesity and diabetes in genetically obese mice by leptin gene therapy. Proc Natl Acad Sci U S A 93:14804-14808.
21. Niswender KD, Morrison CD, Clegg DJ, Olson R, Baskin DG, Myers MG Jr, Seeley RJ, Schwartz MW (2003) Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. Diabetes 52:227-231.
22. Obici S, Feng Z, Karkanias G, Baskin DG, Rossetti L (2002a) Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci 5:566-572.
23. Obici S, Zhang BB, Karkanias G, Rossetti L (2002b) Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 8:1376-1382.
24. Okamoto H, Nakae J, Kitamura T, Park BC, Dragatsis I, Accili D (2004) Transgenic rescue of insulin receptor-deficient mice. J Clin Invest 114:214-223.
25. Okamoto H, Obici S, Accili D, Rossetti L (2005) Restoration of liver insulin signaling in Insr knockout mice fails to normalize hepatic insulin action. J Clin Invest 115:1314-1322. (Pubitemid 40629051)
26. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540-543.
27. Pocai A, Obici S, Schwartz GJ, Rossetti L (2005) A brain-liver circuit regulates glucose homeostasis. Cell Metab 1:53-61.
28. Quennell JH, Mulligan AC, Tups A, Liu X, Phipps SJ, Kemp CJ, Herbison AE, Grattan DR, Anderson GM (2009) Leptin indirectly regulates gonadotropin- releasing hormone neuronal function. Endocrinology 150:2805-2812.
29. Schwartz MW, Baskin DG, Bukowski TR, Kuijper JL, Foster D, Lasser G, Prunkard DE, Porte D Jr, Woods SC, Seeley RJ, Weigle DS (1996) Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes 45:531-535.
30. Segal KR, Landt M, Klein S (1996) Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes 45:988-991.
31. Solomon G, Niv-Spector L, Gonen-Berger D, Callebaut I, Djiane J, Gertler A (2006) Preparation of leptin antagonists by site-directed mutagenesis of human, ovine, rat, and mouse leptin's site III. Ann NY Acad Sci 1091:531-539.
32. Taguchi A, Wartschow LM, White MF (2007) Brain IRS2 signaling coordinates life span and nutrient homeostasis. Science 317:369-372.
33. Tups A, Anderson GM, Rizwan M, Augustine RA, Chaussade C, Shepherd PR, Grattan DR (2010) Both p110α and p110β isoforms of phosphatidylinositol 3-OH-kinase are required for insulin signalling in the hypothalamus. J Neuroendocrinol 22:534-542.
34. Williams KW, Margatho LO, Lee CE, Choi M, Lee S, Scott MM, Elias CF, Elmquist JK (2010) Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J Neurosci 30:2472-2479.
35. Yamada M, Ohnishi H, Sano S, Nakatani A, Ikeuchi T, Hatanaka H (1997) Insulin receptor substrate (IRS)-1 and IRS-2 are tyrosine-phosphorylated and associated with phosphatidylinositol 3-kinase in response to brain-derived neurotrophic factor in cultured cerebral cortical neurons. J Biol Chem 272:30334-30339.
36. Yu X, Park BH, Wang MY, Wang ZV, Unger RH (2008) Making insulin-deficient type 1 diabetic rodents thrive without insulin. Proc Natl Acad Sci U S A 105:14070-14075.
37. Zhang J, Matheny MK, Tümer N, Mitchell MK, Scarpace PJ (2007) Leptin antagonist reveals that the normalization of caloric intake and the thermic effect of food after high-fat feeding are leptin dependent. Am J Physiol Regul Integr Comp Physiol 292:R868-R874.
38. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425-432.