FOXO1 in the ventromedial hypothalamus regulates energy balance

Journal of Clinical Investigation

Volumn 122, Issue 7, 2012, Pages 2578-2589

  Kim, Ki Woo ^a   Donato, Jose ^a   Berglund, Eric D ^a   Choi, Yun Hee ^a   Kohno, Daisuke ^a   Elias, Carol F ^a   DePinho, Ronald A ^b   Elmquist, Joel K ^a  

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

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LEPTIN; STEROIDOGENIC FACTOR 1; TRANSCRIPTION FACTOR FKHR;

ARTICLE; CONTROLLED STUDY; DIET RESTRICTION; ENERGY BALANCE; ENERGY EXPENDITURE; GENE EXPRESSION PROFILING; GENE SEQUENCE; GLUCOSE HOMEOSTASIS; GLUCOSE TOLERANCE; HEART; HYPOTHALAMUS VENTROMEDIAL NUCLEUS; INSULIN SENSITIVITY; MALE; MOUSE; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; SKELETAL MUSCLE; TRANSCRIPTION REGULATION;

EID: 84863549071     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI62848     Document Type: Article

References (47)

1. Nakae J, et al. Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet. 2002;32(2):245-253.
2. Kitamura T, et al. Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake. Nat Med. 2006;12(5):534-540.
3. Ogg S, et al. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature. 1997; 389(6654):994-999. (Pubitemid 27485694)
4. Lin K, Dorman JB, Rodan A, Kenyon C. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science. 1997;278(5341):1319-1322. (Pubitemid 27495748)
5. Nakae J, Kitamura T, Kitamura Y, Biggs WH 3rd, Arden KC, Accili D. The forkhead transcription factor Foxo1 regulates adipocyte differentiation. Dev Cell. 2003;4(1):119-129. (Pubitemid 36105338)
6. Matsumoto M, Pocai A, Rossetti L, Depinho RA, Accili D. Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxo1 in liver. Cell Metab. 2007;6(3):208-216. (Pubitemid 47336849)
7. Kim MS, et al. Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis. Nat Neurosci. 2006;9(7):901-906.
8. Plum L, et al. The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. Nat Med. 2009;15(10):1195-1201.
9. Cao Y, et al. PDK1-Foxo1 in agouti-related peptide neurons regulates energy homeostasis by modulating food intake and energy expenditure. PloS One. 2011;6(4):e18324.
10. Balthasar N, et al. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron. 2004;42(6):983-991. (Pubitemid 38798236)
11. Scott MM, Williams KW, Rossi J, Lee CE, Elmquist JK. Leptin receptor expression in hindbrain Glp-1 neurons regulates food intake and energy balance in mice. J Clin Invest. 2011;121(6):2413-2421.
12. Dhillon H, et al. Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron. 2006;49(2):191-203. (Pubitemid 43089637)
13. King BM. The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav. 2006; 87(2):221-244. (Pubitemid 43188818)
14. Amir S. Intra-ventromedial hypothalamic injection of glutamate stimulates brown adipose tissue thermogenesis in the rat. Brain research. 1990; 511(2):341-344. (Pubitemid 20092024)
15. Bingham NC, Anderson KK, Reuter AL, Stallings NR, Parker KL. Selective loss of leptin receptors in the ventromedial hypothalamic nucleus results in increased adiposity and a metabolic syndrome. Endocrinology. 2008;149(5):2138-2148. (Pubitemid 351574486)
16. Klöckener T, et al. High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons. Nat Neurosci. 2011;14(7):911-918.
17. Minokoshi Y, Saito M, Shimazu T. Sympathetic denervation impairs responses of brown adipose tissue to VMH stimulation. Am J Physiol. 1986; 251(5 pt 2):R1005-R1008.
18. Rothwell NJ, Stock MJ. A role for brown adipose tissue in diet-induced thermogenesis. Nature. 1979; 281(5726):31-35. (Pubitemid 9247988)
19. Majdic G, et al. Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. Endocrinology. 2002;143(2):607-614. (Pubitemid 34107215)
20. Xu Y, et al. PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis. Cell Metab. 2010;12(1):88-95.
21. Paik JH, et al. FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell. 2007;128(2):309-323.
22. Hill JW, et al. Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metab. 2010;11(4):286-297.
23. Kim KW, et al. Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus. Proc Natl Acad Sci U S A. 2011; 108(26):10673-10678.
24. 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 Metab. 2005;2(6):411-420.
25. Scarpace PJ, Matheny M, Pollock BH, Tumer N. Leptin increases uncoupling protein expression and energy expenditure. Am J Physiol. 1997; 273(1 pt 1):E226-E230.
26. Toda C, et al. Distinct effects of leptin and a melanocortin receptor agonist injected into medial hypothalamic nuclei on glucose uptake in peripheral tissues. Diabetes. 2009;58(12):2757-2765.
27. Enriori PJ, Sinnayah P, Simonds SE, Garcia Rudaz C, Cowley MA. Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown adipose tissue in spite of systemic leptin resistance. J Neurosci. 2011;31(34):12189-12197.
28. Lowell BB, Spiegelman BM. Towards a molecular understanding of adaptive thermogenesis. Nature. 2000;404(6778):652-660. (Pubitemid 30205070)
29. Niijima A, Rohner-Jeanrenaud F, Jeanrenaud B. Role of ventromedial hypothalamus on sympathetic efferents of brown adipose tissue. Am J Physiol. 1984;247(4 pt 2):R650-R654. (Pubitemid 15200520)
30. Kageyama H, et al. Fasting increases gene expressions of uncoupling proteins and peroxisome proliferator-activated receptor-gamma in brown adipose tissue of ventromedial hypothalamuslesioned rats. Life Sci. 2003;72(26):3035- 3046. (Pubitemid 36426935)
31. Ahima RS, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382(6588):250-252.
32. Fukuda M, et al. Monitoring FoxO1 localization in chemically identified neurons. J Neurosci. 2008;28(50):13640-13648.
33. Niswender KD, Morton GJ, Stearns WH, Rhodes CJ, Myers MG Jr, Schwartz MW. Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature. 2001;413(6858):794-795. (Pubitemid 33026839)
34. Minokoshi Y, Haque MS, Shimazu T. Microinjection of leptin into the ventromedial hypothalamus increases glucose uptake in peripheral tissues in rats. Diabetes. 1999;48(2):287-291. (Pubitemid 29061100)
35. Ramadori G, et al. SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. Cell Metab. 2011;14(3):301-312.
36. Musatov S, et al. Silencing of estrogen receptor alpha in the ventromedial nucleus of hypothalamus leads to metabolic syndrome. Proc Natl Acad Sci U S A. 2007;104(7):2501-2506. (Pubitemid 46391425)
37. Rios M, et al. Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol. 2001;15(10):1748-1757. (Pubitemid 32939305)
38. Buettner C, et al. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat Med. 2008;14(6):667-675. (Pubitemid 351809549)
39. Morton GJ, Schwartz MW. Leptin and the central nervous system control of glucose metabolism. Physiol Rev. 2011;91(2):389-411.
40. Bates SH, Kulkarni RN, Seifert M, Myers MG Jr. Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis. Cell Metab. 2005;1(3):169-178. (Pubitemid 43960601)
41. Shiuchi T, et al. Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system. Cell Metab. 2009;10(6):466-480.
42. Haque MS, Minokoshi Y, Hamai M, Iwai M, Horiuchi M, Shimazu T. Role of the sympathetic nervous system and insulin in enhancing glucose uptake in peripheral tissues after intrahypothalamic injection of leptin in rats. Diabetes. 1999;48(9):1706-1712. (Pubitemid 29415187)
43. Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature. 1997; 389(6649):374-377. (Pubitemid 27415217)
44. Keen-Rhinehart E, Kalra SP, Kalra PS. AAV-mediated leptin receptor installation improves energy balance and the reproductive status of obese female Koletsky rats. Peptides. 2005;26(12):2567-2578. (Pubitemid 41676733)
45. Warne JP, et al. Impairment of central leptin-mediated PI3K signaling manifested as hepatic steatosis independent of hyperphagia and obesity. Cell Metab. 2011;14(6):791-803.
46. Kim KW, Jo YH, Zhao L, Stallings NR, Chua SC Jr, Parker KL. Steroidogenic factor 1 regulates expression of the cannabinoid receptor 1 in the ventromedial hypothalamic nucleus. Mol Endocrinol. 2008; 22(8):1950-1961.
47. Zhao L, et al. Central nervous system-specific knockout of steroidogenic factor 1 results in increased anxiety-like behavior. Mol Endocrinol. 2008; 22(6):1403-1415. (Pubitemid 351787000)