Artículos de revistas
The Hypothalamic Control Of Feeding And Thermogenesis - Implications On The Development Of Obesity [o Controle Hipotalâmico Da Fome E Da Termogênese - Implicações No Desenvolvimento Da Obesidade]
Registro en:
Arquivos Brasileiros De Endocrinologia E Metabologia. , v. 50, n. 2, p. 165 - 176, 2006.
42730
10.1590/S0004-27302006000200003
2-s2.0-33744467955
Autor
Velloso L.A.
Institución
Resumen
The worldwide increase in the prevalence of obesity is becoming one of the most important clinical-epidemiological phenomena of the present days. Environmental factors such as changes in life-style and feeding behavior associated with poorly characterized genetic determinants are though to play the most important roles in the pathogenesis of this disease. During the last ten years, since the discovery of leptin, great advances were obtained in the characterization of the hypothalamic mechanisms involved in the control of food intake and thermogenesis. Such advances are unveiling a complex and integrated system and are opening a wide perspective for the finding of novel therapeutic targets for the treatment of this harming condition. This review will present some of the most recent findings in this field. It will be focused on the actions of leptin and insulin in the hypothalamus and will explore the hypothesis that hypothalamic resistance to the action of these hormones may play a role in the development of obesity and may act as a molecular link between obesity, type 2 diabetes mellitus and other clinical conditions on which insulin resistance plays an important pathogenetic role. 50 2 165 176 Mayer, J., Obesity (1972) Postgrad Med, 51, pp. 66-69 Baskin, M.L., Ard, J., Franklin, F., Allison, D.B., Prevalence of obesity in the United States (2005) Obes Rev, 6, pp. 5-7 Uauy, R., Albala, C., Kain, J., Obesity trends in Latin America: Transiting from under- To overweight (2001) J Nutr, 131, pp. 893S-9 Kopelman, P.G., Obesity as a medical problem (2000) Nature, 404, pp. 635-643 Costa, M.B., Ferreira, S.R., Franco, L.J., Gimeno, S.G., Iunes, M., Dietary patterns in a high-risk population for glucose intolerance (2000) J Epidemiol, 10, pp. 111-117. , Japanese-Brazilian Diabetes Study Group Ferreira, S.R., Lerario, D.D., Gimeno, S.G., Sanudo, A., Franco, L.J., Obesity and central adiposity in Japanese immigrants: Role of the Western dietary pattern (2002) J Epidemiol, 12, pp. 431-438 Freire, R.D., Cardoso, M.A., Shinzato, A.R., Ferreira, S.R., Nutritional status of Japanese-Brazilian subjects: Comparison across gender and generation (2003) Br J Nutr, 89, pp. 705-713 Foster, G.D., Makris, A.P., Bailer, B.A., Behavioral treatment of obesity (2005) Am J Clin Nutr, 82, pp. 230S-5 Moyers, S.B., Medications as adjunct therapy for weight loss: Approved and off-label agents in use (2005) J Am Diet Assoc, 105, pp. 948-959 Zhang, Y., Proença, R., Maffei, M., Barone, M., Leopold, L., Friedman, J.M., Positional cloning of the mouse obese gene and its human homologue (1994) Nature, 372, pp. 425-432 Tartaglia, L.A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Identification and expression cloning of a leptin receptor, OB-R (1995) Cell, 83, pp. 1263-1271 Tartaglia, L.A., The leptin receptor (1997) J Biol Chem, 272, pp. 6093-6096 Chua Jr., S.C., Chung, W.K., Wu-Peng, X.S., Zhang, Y., Liu, S.M., Tartaglia, L., Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor (1996) Science, 271, pp. 994-996 Bjorbaek, C., Uotani, S., Da Silva, B., Flier, J.S., Divergent signaling capacities of the long and short isoforms of the leptin receptor (1997) J Biol Chem, 272, pp. 32686-32695 Zabeau, L., Lavens, D., Peelman, F., Eyckerman, S., Vandekerckhove, J., Tavernier, J., The ins and outs of leptin receptor activation (2003) FEBS Lett, 546, pp. 45-50 Munzberg, H., Myers Jr., M.G., Molecular and anatomical determinants of central leptin resistance (2005) Nat Neurosci, 8, pp. 566-570 Kellerer, M., Koch, M., Metzinger, E., Mushack, J., Capp, E., Haring, H.U., Leptin activates PI-3 kinase in C2C12 myotubes via janus kinase-2 (JAK-2) and insulin receptor substrate-2 (IRS-2) dependent pathways (1997) Diabetologia, 40, pp. 1358-1362 Xu, A.W., Kaelin, C.B., Takeda, K., Akira, S., Schwartz, M.W., Barsh, G.S., PI3K integrates the action of insulin and leptin on hypothalamic neurons (2005) J Clin Invest, 115, pp. 951-958 Bjorbaek, C., Buchholz, R.M., Davis, S.M., Bates, S.H., Pierroz, D.D., Gu, H., Divergent roles of SHP-2 in ERK activation by leptin receptors (2001) J Biol Chem, 276, pp. 4747-4755 Bjorbaek, C., Kahn, B.B., Leptin signaling in the central nervous system and the periphery (2004) Recent Prog Horm Res, 59, pp. 305-331 Carvalheira, J.B., Siloto, R.M., Ignacchitti, I., Brenelli, S.L., Carvalho, C.R., Leite, A., Insulin modulates leptin-induced STAT3 activation in rat hypothalamus (2001) FEBS Lett, 500, pp. 119-124 Carvalheira, J.B., Ribeiro, E.B., Folli, F., Velloso, L.A., Saad, M.J., Interaction between leptin and insulin signaling pathways differentially affects JAK-STAT and PI 3-kinase-mediated signaling in rat liver (2003) Biol Chem, 384, pp. 151-159 Carvalheira, J.B., Torsoni, M.A., Ueno, M., Amaral, M.E., Araújo, E.P., Velloso, L.A., Cross-talk between the insulin and leptin signalling systems in rat hypothalamus (2005) Obes Res, 13, pp. 48-57 Kasuga, M., Karlsson, F.A., Kahn, C.R., Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor (1982) Science, 215, pp. 185-187 Saltiel, A.R., Kahn, C.R., Insulin signalling and the regulation of glucose and lipid metabolism (2001) Nature, 414, pp. 799-806 Margolis, R.U., Altszuler, N., Insulin in the cerebrospinal fluid (1967) Nature, 215, pp. 1375-1376 Havrankova, J., Roth, J., Brownstein, M.J., Concentrations of insulin and insulin receptors in the brain are independent of peripheral insulin levels. Studies of obese and streptozotocin-treated rodents (1979) J Clin Invest, 64, pp. 636-642 Woods, S.C., Lotter, E.C., McKay, L.D., Porte Jr., D., Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons (1979) Nature, 282, pp. 503-505 White, M.F., The insulin signaling system and the IRS proteins (1997) Diabetologia, 40 (2 SUPPL.), pp. S2-17 Torsoni, M.A., Carvalheira, J.B., Pereira Da Silva, M., De Carvalho-Filho, M.A., Saad, M.J., Velloso, L.A., Molecular and functional resistance to insulin in hypothalamus of rats exposed to cold (2003) Am J Physiol Endocrinol Metab, 285, pp. E216-23 Carvalheira, J.B., Ribeiro, E.B., Araújo, E.P., Guimarães, R.B., Telles, M.M., Torsoni, M., Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats (2003) Diabetologia, 46, pp. 1629-1640 Plum, L., Schubert, M., Bruning, J.C., The role of insulin receptor signaling in the brain (2005) Trends Endocrinol Metab, 16, pp. 59-65 Saad, M.J., Carvalho, C.R., Thirone, A.C., Velloso, L.A., Insulin induces tyrosine phosphorylation of JAK2 in insulin-sensitive tissues of the intact rat (1996) J Biol Chem, 271, pp. 22100-22104 Sivitz, W.I., Walsh, S.A., Morgan, D.A., Thomas, M.J., Haynes, W.G., Effects of leptin on insulin sensitivity in normal rats (1997) Endocrinology, 138, pp. 3395-3401 Flier, J.S., Obesity wars: Molecular progress confronts an expanding epidemic (2004) Cell, 116, pp. 337-350 Folli, F., Bonfanti, L., Renard, E., Kahn, C.R., Merighi, A., Insulin receptor substrate-1 (IRS-1) distribution in the rat central nervous system (1994) J Neurosci, 14, pp. 6412-6422 De, L.A.F.M.L., Saad, M.J., Velloso, L.A., Insulin induces tyrosine phosphorylation of the insulin receptor and SHC, and SHC/GRB2 association in cerebellum but not in forebrain cortex of rats (1999) Brain Res, 826, pp. 74-82 Schwartz, M.W., Woods, S.C., Porte Jr., D., Seeley, R.J., Baskin, D.G., Central nervous system control of food intake (2000) Nature, 404, pp. 661-671 Pereira Da Silva, M., Torsoni, M.A., Nourani, H.V., Augusto, V.D., Souza, C.T., Gasparetti, A.L., Hypothalamic melanin-concentrating hormone is induced by cold exposure and participates in the control of energy expenditure in rats (2003) Endocrinology, 144, pp. 4831-4840 Nandi, A., Kitamura, Y., Kahn, C.R., Accili, D., Mouse models of insulin resistance (2004) Physiol Rev, 84, pp. 623-647 Snyder, E.E., Walts, B., Perusse, L., Chagnon, Y.C., Weisnagel, S.J., Rankinen, T., The human obesity gene map: The 2003 update (2004) Obes Res, 12, pp. 369-439 Eckel, R.H., Grundy, S.M., Zimmet, P.Z., The metabolic syndrome (2005) Lancet, 365, pp. 1415-1428 Radziuk, J., Insulin sensitivity and its measurement: Structural commonalities among the methods (2000) J Clin Endocrinol Metab, 85, pp. 4426-4433 Prada, P.O., Zecchin, H.G., Gasparetti, A.L., Torsoni, M.A., Ueno, M., Hirata, A.E., Western diet modulates insulin signaling, c-Jun N-terminal kinase activity, and insulin receptor substrate-1ser307 phosphorylation in a tissue-specific fashion (2005) Endocrinology, 146, pp. 1576-1587 Araújo, E.P., De Souza, C.T., Gasparetti, A.L., Ueno, M., Boschero, A.C., Saad, M.J., Short-term in vivo inhibition of insulin receptor substrate-1 expression leads to insulin resistance, hyperinsulinemia, and increased adiposity (2005) Endocrinology, 146, pp. 1428-1437 Hileman, S.M., Pierroz, D.D., Masuzaki, H., Bjorbaek, C., El-Haschimi, K., Banks, W.A., Characterization of short isoforms of the leptin receptor in rat cerebral microvessels and of brain uptake of leptin in mouse models of obesity (2002) Endocrinology, 143, pp. 775-783 Caro, J.F., Kolaczynski, J.W., Nyce, M.R., Ohannesian, J.P., Opentanova, I., Goldman, W.H., Decreased cerebrospinal-fluid/serum leptin ratio in obesity: A possible mechanism for leptin resistance (1996) Lancet, 348, pp. 159-161 Banks, W.A., Jaspan, J.B., Huang, W., Kastin, A.J., Transport of insulin across the blood-brain barrier: Saturability at euglycemic doses of insulin (1997) Peptides, 18, pp. 1423-1429 Kaiyala, K.J., Prigeon, R.L., Kahn, S.E., Woods, S.C., Schwartz, M.W., Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs (2000) Diabetes, 49, pp. 1525-1533 Yiannakouris, N., Yannakoulia, M., Melistas, L., Chan, J.L., Klimis-Zacas, D., Mantzoros, C.S., The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability (2001) J Clin Endocrinol Metab, 86, pp. 4434-4439 Clement, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction (1998) Nature, 392, pp. 398-401 Paracchini, V., Pedotti, P., Taioli, E., Genetics of leptin and obesity: A HuGE review (2005) Am J Epidemiol, 162, pp. 101-114 Kosztolanyi, G., Leprechaunism/Donohue syndrome/insulin receptor gene mutations: A syndrome delineation story from clinicopathological description to molecular understanding (1997) Eur J Pediatr, 156, pp. 253-255 Taylor, S.I., Kadowaki, T., Kadowaki, H., Accili, D., Cama, A., McKeon, C., Mutations in insulin-receptor gene in insulin-resistant patients (1990) Diabetes Care, 13, pp. 257-279 Bruning, J.C., Gautam, D., Burks, D.J., Gillette, J., Schubert, M., Orban, P.C., Role of brain insulin receptor in control of body weight and reproduction (2000) Science, 289, pp. 2122-2125 El-Haschimi, K., Pierroz, D.D., Hileman, S.M., Bjorbaek, C., Flier, J.S., Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity (2000) J Clin Invest, 105, pp. 1827-1832 Alexander, W.S., Hilton, D.J., The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response (2004) Annu Rev Immunol, 22, pp. 503-529 Bjorbaek, C., El-Haschimi, K., Frantz, J.D., Flier, J.S., The role of SOCS-3 in leptin signaling and leptin resistance (1999) J Biol Chem, 274, pp. 30059-30065 Howard, J.K., Cave, B.J., Oksanen, L.J., Tzameli, I., Bjorbaek, C., Flier, J.S., Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3 (2004) Nat Med, 10, pp. 734-738 De Souza, C.T., Araújo, E.P., Bordin, S., Ashimine, R., Zollner, R.L., Boschero, A.C., Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus (2005) Endocrinology, 146, pp. 4192-4199 Kohn, L.D., Wallace, B., Schwartz, F., McCall, K., Is type 2 diabetes an autoimmune-inflammatory disorder of the innate immune system? (2005) Endocrinology, 146, pp. 4189-4191 Neel, B.G., Gu, H., Pao, L., The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling (2003) Trends Biochem Sci, 28, pp. 284-293 Zhang, E.E., Chapeau, E., Hagihara, K., Feng, G.S., Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism (2004) Proc Natl Acad Sci USA, 101, pp. 16064-16069