The PI3K signaling pathway mediates the biological effects of leptin;A via de sinalização intracelular da PI3K medeia os efeitos biológicos da leptina

Arquivos Brasileiros de Endocrinologia e Metabologia

Volumn 54, Issue 7, 2010, Pages 591-602

  Donato Jr , Jose ^a   Frazão, Renata ^a   Elias, Carol Fuzeti ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Akt; Energy balance; Hypothalamus; Insulin; Phosphatidylinositol; Phosphatidylinositol 3 kinases

Indexed keywords

EID: 78649464963     PISSN: 00042730     EISSN: 16779487     Source Type: Journal    
DOI: 10.1590/s0004-27302010000700002     Document Type: Review

References (60)

1. Ward S, Sotsios Y, Dowden J, Bruce I, Finan P. Therapeutic potential of phosphoinositide 3-kinase inhibitors. Chem Biol. 2003;10(3):207-13.
2. Knight ZA, Gonzalez B, Feldman ME, Zunder ER, Goldenberg DD, Williams O, et al. A pharmacological map of the PI3-K family defines a role for p110[alpha] in insulin signaling. Cell. 2006;125(4):733-47.
3. Jia S, Roberts TM, Zhao JJ. Should individual PI3 kinase isoforms be targeted in cancer? Curr Opin Cell Biol. 2009;21(2):199-208.
4. Myers MG Jr, Backer JM, Sun XJ, Shoelson S, Hu P, Schlessinger J, et al. IRS-1 activates phosphatidylinositol 3'-kinase by associating with src homology 2 domains of p85. Proc Natl Acad Sci U S A. 1992;89(21):10350-4.
5. Williams KW, Scott MM, Elmquist JK. From observation to experimentation: leptin action in the mediobasal hypothalamus. Am J Clin Nutr. 2009;89(3):985S-90S.
6. Schwartz MW. Central nervous system regulation of food intake. Obesity (Silver Spring). 2006;14 Suppl 1:1S-8S.
7. Simpson KA, Martin NM, Bloom SR. Hypothalamic regulation of food intake and clinical therapeutic applications. Arq Bras Endocrinol Metabol. 2009;53(2):120-8.
8. Ribeiro SM, dos Santos ZA, da Silva RJ, Louzada E, Donato J Jr, Tirapegui J. [Leptin: aspects on energetic balance, physical exercise and athletic amenorhea]. Arq Bras Endocrinol Metabol. 2007;51(1):11-24.
9. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269(5223):543-6.
10. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest. 2002;110(8):1093-103.
11. Licinio J, Caglayan S, Ozata M, Yildiz BO, de Miranda PB, O'Kirwan F, et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptindeficient adults. Proc Natl Acad Sci U S A. 2004;101(13):4531-6.
12. de Luca C, Kowalski TJ, Zhang Y, Elmquist JK, Lee C, Kilimann MW, et al. Complete rescue of obesity, diabetes, and infertility in db/db mice by neuron-specific LEPR-B transgenes. J Clin Invest. 2005;115(12):3484-93.
13. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos- Flier E, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382(6588):250-2.
14. Schwartz MW, Seeley RJ, Woods SC, Weigle DS, Campfield LA, Burn P, et al. Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes. 1997;46(12):2119-23.
15. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83(7):1263-71.
16. Chua SC, Koutras IK, Han L, Liu S-M, Kay J, Young SJ, et al. Fine structure of the murine leptin receptor gene: splice site suppression is required to form two alternatively spliced transcripts. Genomics. 1997;45(2):264-70.
17. Myers MG Jr. Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res. 2004;59:287-304.
18. Bates SH, Stearns WH, Dundon TA, Schubert M, Tso AW, Wang Y, et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature. 2003;421(6925):856-9.
19. Scott MM, Lachey JL, Sternson SM, Lee CE, Elias CF, Friedman JM, et al. Leptin targets in the mouse brain. J Comp Neurol. 2009;514(5):518-32.
20. Donato J Jr, Silva RJ, Sita LV, Lee S, Lee C, Lacchini S, et al. The ventral premammillary nucleus links fasting-induced changes in leptin levels and coordinated luteinizing hormone secretion. J Neurosci. 2009;29(16):5240-50.
21. Bjorbaek C, Elmquist JK, Frantz JD, Shoelson SE, Flier JS. Identification of SOCS-3 as a potential mediator of central leptin resistance. Molecular Cell. 1998;1(4):619-25.
22. Howard JK, Flier JS. Attenuation of leptin and insulin signaling by SOCS proteins. Trends Endocrinol Metab. 2006;17(9):365-71.
23. Glaum SR, Hara M, Bindokas VP, Lee CC, Polonsky KS, Bell GI, et al. Leptin, the obese gene product, rapidly modulates synaptic transmission in the hypothalamus. Mol Pharmacol. 1996;50(2):230-5.
24. Spanswick D, Smith MA, Groppi VE, Logan SD, Ashford ML. Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature. 1997;390(6659):521-5.
25. Xu AW, Kaelin CB, Takeda K, Akira S, Schwartz MW, Barsh GS. PI3K integrates the action of insulin and leptin on hypothalamic neurons. J Clin Invest. 2005;115(4):951-8.
26. Hill JW, Williams KW, Ye C, Luo J, Balthasar N, Coppari R, et al. Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice. J Clin Invest. 2008;118(5):1796-805.
27. Cowley MA, Smart JL, Rubinstein M, Cerdan MG, Diano S, Horvath TL, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature. 2001;411(6836):480-4.
28. Niswender KD, Morton GJ, Stearns WH, Rhodes CJ, Myers MG Jr, Schwartz MW. Intracellular signalling. Key enzyme in leptininduced anorexia. Nature. 2001;413(6858):794-5.
29. Zhao AZ, Huan JN, Gupta S, Pal R, Sahu A. A phosphatidylinositol 3-kinase phosphodiesterase 3B-cyclic AMP pathway in hypothalamic action of leptin on feeding. Nat Neurosci. 2002;5(8):727-8.
30. Morrison CD, Morton GJ, Niswender KD, Gelling RW, Schwartz MW. Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signaling. Am J Physiol Endocrinol Metab. 2005;289(6):E1051-7.
31. Niswender KD, Morrison CD, Clegg DJ, Olson R, Baskin DG, Myers MG Jr, et al. Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: a key mediator of insulin-induced anorexia. Diabetes. 2003;52(2):227-31.
32. Morton GJ, Gelling RW, Niswender KD, Morrison CD, Rhodes CJ, Schwartz MW. Leptin regulates insulin sensitivity via phosphatidylinositol- 3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metabolism. 2005;2(6):411-20.
33. Roman EAFR, Reis D, Romanatto T, Maimoni D, Ferreira EA, Santos GA, et al. Central leptin action improves skeletal muscle AKT, AMPK, and PGC1[alpha] activation by hypothalamic PI3K-dependent mechanism. Mol Cell Endocrinol. 2010;314(1):62-9.
34. Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol. 2010;11(5):329-41.
35. Ueki K, Yballe CM, Brachmann SM, Vicent D, Watt JM, Kahn CR, et al. Increased insulin sensitivity in mice lacking p85beta subunit of phosphoinositide 3-kinase. Proc Natl Acad Sci U S A. 2002;99(1):419-24.
36. Chen D, Mauvais-Jarvis F, Bluher M, Fisher SJ, Jozsi A, Goodyear LJ, et al. p50alpha/p55alpha phosphoinositide 3-kinase knockout mice exhibit enhanced insulin sensitivity. Mol Cell Biol. 2004;24(1):320-9.
37. Fruman DA, Mauvais-Jarvis F, Pollard DA, Yballe CM, Brazil D, Bronson RT, et al. Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha. Nat Genet. 2000;26(3):379-82.
38. Mauvais-Jarvis F, Ueki K, Fruman DA, Hirshman MF, Sakamoto K, Goodyear LJ, et al. Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. J Clin Invest. 2002;109(1):141-9.
39. Terauchi Y, Tsuji Y, Satoh S, Minoura H, Murakami K, Okuno A, et al. Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. Nat Genet. 1999;21(2):230-5.
40. Hill JW, Xu Y, Preitner F, Fukuda M, Cho Y-R, Luo J, et al. Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis. Endocrinology. 2009;150(11):4874-82.
41. Okkenhaug K, Bilancio A, Farjot G, Priddle H, Sancho S, Peskett E, et al. Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice. Science. 2002;297(5583):1031-4.
42. Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, et al. p110M, a novel phosphoinositide 3-kinase in leukocytes. Proc Natl Acad Sci U S A. 1997;94(9):4330-5.
43. Bi L, Okabe I, Bernard DJ, Nussbaum RL. Early embryonic lethality in mice deficient in the p110beta catalytic subunit of PI 3-kinase. Mamm Genome. 2002;13(3):169-72.
44. Bi L, Okabe I, Bernard DJ, Wynshaw-Boris A, Nussbaum RL. Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110alpha subunit of phosphoinositide 3-kinase. J Biol Chem. 1999;274(16):10963-8.
45. Foukas LC, Claret M, Pearce W, Okkenhaug K, Meek S, Peskett E, et al. Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature. 2006;441(7091):366-70.
46. Zhao JJ, Cheng H, Jia S, Wang L, Gjoerup OV, Mikami A, et al. The p110TTisoform of PI3K is essential for proper growth factor signaling and oncogenic transformation. Proc Natl Acad Sci U S A. 2006;103(44):16296-300.
47. Xu Y, Hill JW, Fukuda M, Gautron L, Sohn J-W, Kim K-W, et al. PI3K Signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis. Cell Metab. 2010;12(1):88-95.
48. Chaussade C, Rewcastle GW, Kendall JD, Denny WA, Cho K, Gronning LM, et al. Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling. Biochem J. 2007;404(3):449-58.
49. Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee SH, et al. Essential roles of PI(3)K-p110ooin cell growth, metabolism and tumorigenesis. Nature. 2008;454(7205):776-9.
50. Ciraolo E, Iezzi M, Marone R, Marengo S, Curcio C, Costa C, et al. Phosphoinositide 3-kinase p110beta activity: key role in metabolism and mammary gland cancer but not development. Sci Signal. 2008;1(36):ra3.
51. Tups A, Anderson GM, Rizwan M, Augustine RA, Chaussade C, Shepherd PR, et al. Both p110alpha and p110beta isoforms of phosphatidylinositol 3-OH-kinase are required for insulin signalling in the hypothalamus. J Neuroendocrinol. 2010;22(6):534-42.
52. Al-Qassab H, Smith MA, Irvine EE, Guillermet-Guibert J, Claret M, Choudhury AI, et al. Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP Neurons Cell Metab. 2009;10(5):343-54.
53. Plum L, Ma X, Hampel B, Balthasar N, Coppari R, Münzberg H, et al. Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity. J Clin Invest. 2006;116(7):1886-901.
54. Plum L, Rother E, Münzberg H, Wunderlich FT, Morgan DA, Hampel B, et al. Enhanced leptin-stimulated Pi3k activation in the CNS promotes white adipose tissue transdifferentiation. Cell Metabolism. 2007;6(6):431-45.
55. Gildea JJ, Herlevsen M, Harding MA, Gulding KM, Moskaluk CA, Frierson HF, et al. PTEN can inhibit in vitro organotypic and in vivo orthotopic invasion of human bladder cancer cells even in the absence of its lipid phosphatase activity. Oncogene. 2004;23(40):6788-97.
56. Gu J, Tamura M, Yamada KM. Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways. J Cell Biol. 1998;143(5):1375-83.
57. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625-38.
58. Osorio-Costa F, Rocha GZ, Dias MM, Carvalheira JB. Epidemiological and molecular mechanisms aspects linking obesity and cancer. Arq Bras Endocrinol Metabol. 2009;53(2):213-26.
59. Huang X-F, Chen J-Z. Obesity, the PI3K/Akt signal pathway and colon cancer. Obesity Reviews. 2009;10(6):610-6.
60. Saxena NK, Sharma D, Ding X, Lin S, Marra F, Merlin D, et al. Concomitant activation of the JAK/STAT, PI3K/AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer Res. 2007;67(6):2497-507.