Minireview: Molecular targets for obesity therapy in the brain

Endocrinology

Volumn 150, Issue 6, 2009, Pages 2512-2517

  Obici, Silvana ^a  

^a UNIVERSITY OF CINCINNATI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE KINASE; ADIPONECTIN; AGOUTI RELATED PROTEIN; ALPHA INTERMEDIN; AMINO ACID; BRAIN DERIVED NEUROTROPHIC FACTOR; CARNITINE PALMITOYLTRANSFERASE I; COENZYME A; FATTY ACID; FATTY ACID SYNTHASE; GHRELIN; GLUCOSE; INSULIN; JANUS KINASE; LEPTIN; LEPTIN RECEPTOR; LIPID; MALONYL COENZYME A DECARBOXYLASE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MELANOCORTIN; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; NEUROPEPTIDE Y; OREXIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROOPIOMELANOCORTIN; STAT3 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING 3;

ADIPOCYTE; APPETITE; ARCUATE NUCLEUS; BLOOD BRAIN BARRIER; BODY WEIGHT; BRAIN; CENTRAL NERVOUS SYSTEM; ENERGY EXPENDITURE; ENERGY METABOLISM; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; FEEDING BEHAVIOR; FOOD INTAKE; GLUCOSE METABOLISM; HOMEOSTASIS; HORMONAL REGULATION; HORMONE RELEASE; HORMONE RESISTANCE; HUMAN; HYPOTHALAMUS; LIPID DIET; LIPID METABOLISM; MACRONUTRIENT; NONHUMAN; OBESITY; PATHOPHYSIOLOGY; PRIORITY JOURNAL; SHORT SURVEY; SIGNAL TRANSDUCTION; VENTRAL TEGMENTUM; WEIGHT REDUCTION;

ANIMALS; BODY WEIGHT; BRAIN; ENERGY METABOLISM; HUMANS; HYPOTHALAMUS; LEPTIN; OBESITY;

EID: 66649112489     PISSN: 00137227     EISSN: 00137227     Source Type: Journal    
DOI: 10.1210/en.2009-0409     Document Type: Short Survey

References (53)

1. Schwartz MW, Porte Jr D 2005 Diabetes, obesity, and the brain. Science 307:375-379 (Pubitemid 40139972)
2. 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 (Pubitemid 24365442)
3. Schwartz MW, Woods SC, Porte Jr D, Seeley RJ, Baskin DG 2000 Central nervous system control of food intake. Nature 404:661-671 (Pubitemid 30205071)
4. Myers MG, Cowley MA, Münzberg H 2008 Mechanisms of leptin action and leptin resistance. Annu Rev Physiol 70:537-556
5. Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL, Cone RD, Low MJ 2001 Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480-484 (Pubitemid 32494394)
6. Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, Barsh GS 1997 Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278:135-138 (Pubitemid 27446294)
7. Butler AA, Cone RD 2003 Knockout studies defining different roles for melanocortin receptors in energy homeostasis. Ann NY Acad Sci 994:240-245 (Pubitemid 36793873)
8. Farooqi IS, Yeo GS, Keogh JM, Aminian S, Jebb SA, Butler G, Cheetham T, O'Rahilly S 2000 Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J Clin Invest 106:271-279 (Pubitemid 30483131)
9. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F 1997 Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88:131-141 (Pubitemid 27180337)
10. Obici S, Feng Z, Tan J, Liu L, Karkanias G, Rossetti L 2001 Central melanocortin receptors regulate insulin action. J Clin Invest 108:1079-1085 (Pubitemid 32946082)
11. Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H, Williams T, Ferreira M, Tang V, McGovern RA, Kenny CD, Christiansen LM, Edelstein E, Choi B, Boss O, Aschkenasi C, Zhang CY, Mountjoy K, Kishi T, Elmquist JK, Lowell BB 2005 Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123:493-505 (Pubitemid 41546678)
12. Abizaid A, Gao Q, Horvath TL 2006 Thoughts for food: brain mechanisms and peripheral energy balance. Neuron 51:691-702 (Pubitemid 44374909)
13. Gropp E, Shanabrough M, Borok E, Xu AW, Janoschek R, Buch T, Plum L, Balthasar N, Hampel B, Waisman A, Barsh GS, Horvath TL, Brüning JC 2005 Agouti-related peptide-expressing neurons are mandatory for feeding. Nat Neurosci 8:1289-1291 (Pubitemid 41630413)
14. Luquet S, Perez FA, Hnasko TS, Palmiter RD 2005 NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science 310:683-685 (Pubitemid 41528162)
15. Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, Tang V, Kenny CD, McGovern RA, Chua Jr SC, Elmquist JK, Lowell BB 2004 Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42:983-991 (Pubitemid 38798236)
16. van de Wall E, Leshan R, Xu AW, Balthasar N, Coppari R, Liu SM, Jo YH, MacKenzie RG, Allison DB, Dun NJ, Elmquist J, Lowell BB, Barsh GS, de Luca C, Myers Jr MG, Schwartz GJ, Chua Jr SC 2008 Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion. Endocrinology 149:1773-1785
17. Dhillon H, Zigman JM, Ye C, Lee CE, McGovern RA, Tang V, Kenny CD, Christiansen LM, White RD, Edelstein EA, Coppari R, Balthasar N, Cowley MA, Chua Jr S, Elmquist JK, Lowell BB 2006 Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron 49:191-203 (Pubitemid 43089637)
18. Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, Reichardt LF 2003 Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 6:736-742 (Pubitemid 36792889)
19. Rios M, Fan G, Fekete C, Kelly J, Bates B, Kuehn R, Lechan RM, Jaenisch R 2001 Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol 15:1748-1757 (Pubitemid 32939305)
20. Unger TJ, Calderon GA, Bradley LC, Sena-Esteves M, Rios M 2007 Selective deletion of Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. J Neurosci 27:14265-14274
21. Ludwig DS, Tritos NA, Mastaitis JW, Kulkarni R, Kokkotou E, Elmquist J, Lowell B, Flier JS, Maratos-Flier E 2001 Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J Clin Invest 107:379-386 (Pubitemid 32157970)
22. Flier JS 2004 Obesity wars: molecular progress confronts an expanding epidemic. Cell 116:337-350 (Pubitemid 38167322)
23. Grill HJ, Schwartz MW, Kaplan JM, Foxhall JS, Breininger J, Baskin DG 2002 Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake. Endocrinology 143:239-246 (Pubitemid 34056425)
24. Williams DL, Bowers RR, Bartness TJ, Kaplan JM, Grill HJ 2003 Brainstem melanocortin 3/4 receptor stimulation increases uncoupling protein gene expression in brown fat. Endocrinology 144:4692-4697 (Pubitemid 37378377)
25. Fulton S, Pissios P, Manchon RP, Stiles L, Frank L, Pothos EN, Maratos-Flier E, Flier JS 2006 Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 51:811-822 (Pubitemid 44374918)
26. Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, Thurmon JJ, Marinelli M, DiLeone RJ 2006 Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 51:801-810 (Pubitemid 44374908)
27. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL 1996 Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292-295 (Pubitemid 26033933)
28. El Haschimi K, Pierroz DD, Hileman SM, Bjørbaek C, Flier JS 2000 Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest 105:1827-1832 (Pubitemid 30421764)
29. Bjorbak C, Lavery HJ, Bates SH, Olson RK, Davis SM, Flier JS, Myers Jr MG 2000 SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem 275:40649-40657 (Pubitemid 32064706)
30. 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 (Pubitemid 44138722)
31. Bence KK, Delibegovic M, Xue B, Gorgun CZ, Hotamisligil GS, Neel BG, Kahn BB 2006 Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat Med 12:917-924 (Pubitemid 44175143)
32. Obici S, Feng Z, Morgan K, Stein D, Karkanias G, Rossetti L 2002 Central administration of oleic acid inhibits glucose production and food intake. Diabetes 51:271-275 (Pubitemid 34764780)
33. Lam TK, Schwartz GJ, Rossetti L 2005 Hypothalamic sensing of fatty acids. Nat Neurosci 8:579-584 (Pubitemid 40594197)
34. Loftus TM, Jaworsky DE, Frehywot GL, Townsend CA, Ronnett GV, Lane MD, Kuhajda FP 2000 Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 288:2379-2381 (Pubitemid 30448165)
35. McGarry JD, Mannaerts GP, Foster DW 1977 A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest 60:265-270 (Pubitemid 8145165)
36. Saha AK, Kurowski TG, Ruderman NB 1995 A malonyl-CoA fuel-sensing mechanism in muscle: effects of insulin, glucose, and denervation. Am J Physiol 269:E283-E289
37. Obici S, Rossetti L 2003 Nutrient sensing and the regulation of insulin action and energy balance. Endocrinology 144:5172-5178 (Pubitemid 37476043)
38. He W, Lam TK, Obici S, Rossetti L 2006 Molecular disruption of hypothalamic nutrient sensing induces obesity. Nat Neurosci 9:227-233 (Pubitemid 43164546)
39. Hu Z, Dai Y, Prentki M, Chohnan S, Lane MD 2005 A role for hypothalamic malonyl-CoA in the control of food intake. J Biol Chem 280:39681-39683 (Pubitemid 41779099)
40. Obici S, Feng Z, Arduini A, Conti R, Rossetti L 2003 Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med 9:756-761 (Pubitemid 36749226)
41. Wolfgang MJ, Lane MD 2006 The role of hypothalamic malonyl-CoA in energy homeostasis. J Biol Chem 281:37265-37269 (Pubitemid 46042029)
42. Gao S, Kinzig KP, Aja S, Scott KA, Keung W, Kelly S, Strynadka K, Chohnan S, Smith WW, Tamashiro KL, Ladenheim EE, Ronnett GV, Tu Y, Birnbaum MJ, Lopaschuk GD, Moran TH 2007 Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake. Proc Natl Acad Sci USA 104:17358-17363 (Pubitemid 350219847)
43. Wolfgang MJ, Cha SH, Sidhaye A, Chohnan S, Cline G, Shulman GI, Lane MD 2007 Regulation of hypothalamic malonyl-CoA by central glucose and leptin. Proc Natl Acad Sci USA 104:19285-19290
44. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferré P, Birnbaum MJ, Stuck BJ, Kahn BB 2004 AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428:569-574 (Pubitemid 38480541)
45. Andersson U, Filipsson K, Abbott CR, Woods A, Smith K, Bloom SR, Carling D, Small CJ 2004 AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem 279:12005-12008 (Pubitemid 38445761)
46. Lee K, Li B, Xi X, Suh Y, Martin RJ 2005 Role of neuronal energy status in the regulation of adenosine 5′-monophosphate-activated protein kinase, orexigenic neuropeptides expression, and feeding behavior. Endocrinology 146:3-10 (Pubitemid 40051714)
47. Claret M, Smith MA, Batterham RL, Selman C, Choudhury AI, Fryer LG, Clements M, Al-Qassab H, Heffron H, Xu AW, Speakman JR, Barsh GS, Viollet B, Vaulont S, Ashford ML, Carling D, Withers DJ 2007 AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J Clin Invest 117:2325-2336 (Pubitemid 47219577)
48. Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC, Seeley RJ 2006 Hypothalamic mTOR signaling regulates food intake. Science 312:927-930 (Pubitemid 43727328)
49. Morrison CD, Xi X, White CL, Ye J, Martin RJ 2007 Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism. Am J Physiol Endocrinol Metab 293:E165-E171
50. Zhang Y, Guo K, LeBlanc RE, Loh D, Schwartz GJ, Yu YH 2007 Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 56:1647-1654 (Pubitemid 46842599)
51. Lenard NR, Berthoud HR 2008 Central and peripheral regulation of food intake and physical activity: pathways and genes. Obesity (Silver Spring) 16(Suppl 3):S11-S22
52. Wang J, Obici S, Morgan K, Barzilai N, Feng Z, Rossetti L 2001 Overfeeding rapidly induces leptin and insulin resistance. Diabetes 50:2786-2791 (Pubitemid 33733130)
53. Morgan K, Obici S, Rossetti L 2004 Hypothalamic responses to long-chain fatty acids are nutritionally regulated. J Biol Chem 279:31139-31148 (Pubitemid 39037776)