Nuclear factor κb (NF-κB) suppresses food intake and energy expenditure in mice by directly activating the Pomc promoter

Diabetologia

Volumn 56, Issue 4, 2013, Pages 925-936

  Shi, X ^a   Wang, X ^a   Li, Q ^a   Su, M ^a   Chew, E ^a   Wong, E T ^b   Lacza, Z ^c   Radda, G K ^a   Tergaonkar, V ^b,d   Han, W ^a,b,d,e  

^a AGENCY FOR SCIENCE   (Singapore)

^b INSTITUTE OF MOLECULAR AND CELL BIOLOGY   (Singapore)

^c SEMMELWEIS UNIVERSITY   (Hungary)

^d NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^e NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

Appetite; Energy homeostasis; FOXO1; Inflammation; NF B; Obesity; STAT3

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LEPTIN; PROOPIOMELANOCORTIN; STAT3 PROTEIN; TRANSCRIPTION FACTOR FKHR; TRANSCRIPTION FACTOR RELA; TRANSCRIPTION FACTOR SP1;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING SITE; CHRONIC INFLAMMATION; CONTROLLED STUDY; DNA METHYLATION; ENERGY EXPENDITURE; FOOD INTAKE; GENE ACTIVATION; GENE ACTIVITY; INFLAMMATION; MALE; MOUSE; NERVE CELL; NONHUMAN; PHYSICAL ACTIVITY; POMC GENE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION;

ANIMALS; BASE SEQUENCE; BEHAVIOR, ANIMAL; EATING; FEEDING BEHAVIOR; GENE EXPRESSION REGULATION; INFLAMMATION; LEPTIN; MALE; MICE; MICE, INBRED C57BL; MOLECULAR SEQUENCE DATA; NF-KAPPA B; PRO-OPIOMELANOCORTIN; PROMOTER REGIONS, GENETIC; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR;

EID: 84876490508     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-013-2831-2     Document Type: Article

References (50)

1. Friedman JM, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763-770
2. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661-671
3. Li C, Friedman JM (1999) Leptin receptor activation of SH2 domain containing protein tyrosine phosphatase 2 modulates Ob receptor signal transduction. Proc Natl Acad Sci U S A 96:9677-9682
4. Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW (2006) Central nervous system control of food intake and body weight. Nature 443:289-295
5. Myers MG Jr, Leibel RL, Seeley RJ, Schwartz MW (2010) Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metabol: TEM 21:643-651
6. Bjorbak C, Lavery HJ, Bates SH et al (2000) SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J Biol Chem 275:40649-40657
7. El-Haschimi K, Pierroz DD, Hileman SM, Bjorbaek C, Flier JS (2000) Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Investig 105:1827-1832
8. Bence KK, Delibegovic M, Xue B et al (2006) Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat Med 12:917-924
9. Elchebly M, Payette P, Michaliszyn E et al (1999) Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 283:1544-1548
10. Yang G, Lim CY, Li C et al (2009) FoxO1 inhibits leptin regulation of pro-opiomelanocortin promoter activity by blocking STAT3 interaction with specificity protein 1. J Biol Chem 284:3719-3727
11. Kim MS, Pak YK, Jang PG et al (2006) Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis. Nat Neurosci 9:901-906
12. Kitamura T, Feng Y, Kitamura YI et al (2006) Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake. Nat Med 12:534-540
13. Grossberg AJ, Scarlett JM, Marks DL (2010) Hypothalamic mechanisms in cachexia. Physiol Behav 100:478-489
14. Kariagina A, Romanenko D, Ren SG, Chesnokova V (2004) Hypothalamic-pituitary cytokine network. Endocrinology 145:104-112
15. Teo H, Ghosh S, Luesch H et al (2010) Telomere-independent Rap1 is an IKK adaptor and regulates NF-kappaB-dependent gene expression. Nat Cell Biol 12:758-767
16. Wu ZH, Wong ET, Shi Y et al (2010) ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress. Mol Cell 40:75-86
17. Arkan MC, Hevener AL, Greten FR et al (2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11:191-198
18. Yuan M, Konstantopoulos N, Lee J et al (2001) Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293:1673-1677
19. Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D (2008) Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 135:61-73
20. Hayden MS, Ghosh S (2008) Shared principles in NF-kappaB signaling. Cell 132:344-362
21. Lou PH, Gustavsson N, Wang Y, Radda GK, Han W (2011) Increased lipolysis and energy expenditure in a mouse model with severely impaired glucagon secretion. PLoS One 6:e26671
22. Lou PH, Yang G, Huang L et al (2010) Reduced body weight and increased energy expenditure in transgenic mice over-expressing soluble leptin receptor. PLoS One 5:e11669
23. Ge H, Huang L, Pourbahrami T, Li C (2002) Generation of soluble leptin receptor by ectodomain shedding of membrane-spanning receptors in vitro and in vivo. J Biol Chem 277:45898-45903
24. Jang PG, Namkoong C, Kang GM et al (2010) NF-kappaB activation in hypothalamic pro-opiomelanocortin neurons is essential in illness- and leptin-induced anorexia. J Biol Chem 285:9706-9715
25. Dong J, Jimi E, Zeiss C, Hayden MS, Ghosh S (2010) Constitutively active NF-kappaB triggers systemic TNFalpha-dependent inflammation and localized TNFalpha-independent inflammatory disease. Genes Dev 24:1709-1717
26. Xu AW, Ste-Marie L, Kaelin CB, Barsh GS (2007) Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. Endocrinology 148:72-80
27. Lee H, Herrmann A, Deng JH et al (2009) Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors. Canc Cell 15:283-293
28. Yang J, Liao X, Agarwal MK, Barnes L, Auron PE, Stark GR (2007) Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFkappaB. Genes Dev 21:1396-1408
29. Yu Z, Kone BC (2004) The STAT3 DNA-binding domain mediates interaction with NF-kappaB p65 and inducible nitric oxide synthase transrepression in mesangial cells. J Am Soc Nephrol 15:585-591
30. Yu Z, Zhang W, Kone BC (2002) Signal transducers and activators of transcription 3 (STAT3) inhibits transcription of the inducible nitric oxide synthase gene by interacting with nuclear factor kappaB. Biochem J 367:97-105
31. Beg AA, Baltimore D (1996) An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 274:782-784
32. Beg AA, Sha WC, Bronson RT, Ghosh S, Baltimore D (1995) Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. Nature 376:167-170
33. Doi TS, Takahashi T, Taguchi O, Azuma T, Obata Y (1997) NF-kappa B RelA-deficient lymphocytes: normal development of T cells and B cells, impaired production of IgA and IgG1 and reduced proliferative responses. J Exp Med 185:953-961
34. Alcamo E, Hacohen N, Schulte LC, Rennert PD, Hynes RO, Baltimore D (2002) Requirement for the NF-kappaB family member RelA in the development of secondary lymphoid organs. J Exp Med 195:233-244
35. Doi TS, Marino MW, Takahashi T et al (1999) Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic lethality. Proc Natl Acad Sci U S A 96:2994-2999
36. Rosenfeld ME, Prichard L, Shiojiri N, Fausto N (2000) Prevention of hepatic apoptosis and embryonic lethality in RelA/TNFR-1 double knockout mice. Am J Pathol 156:997-1007
37. De Souza CT, Araujo EP, Bordin S et al (2005) Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146:4192-4199
38. Bird A (2007) Perceptions of epigenetics. Nature 447:396-398
39. Newell-Price J, King P, Clark AJ (2001) The CpG island promoter of the human proopiomelanocortin gene is methylated in nonexpressing normal tissue and tumors and represses expression. Mol Endocrinol (Baltimore MD) 15:338-348
40. Stevens A, Begum G, Cook A et al (2010) Epigenetic changes in the hypothalamic proopiomelanocortin and glucocorticoid receptor genes in the ovine fetus after periconceptional undernutrition. Endocrinology 151:3652-3664
41. Plagemann A, Harder T, Brunn M et al (2009) Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding: an epigenetic model of obesity and the metabolic syndrome. J Physiol 587:4963-4976
42. Ye L, Li X, Kong X et al (2005) Hypomethylation in the promoter region of POMC gene correlates with ectopic overexpression in thymic carcinoids. J Endocrinol 185:337-343
43. Berglund ED, Vianna CR, Donato J Jr et al (2012) Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J Clin Investig 122:1000-1009
44. Millington GW (2007) The role of proopiomelanocortin (POMC) neurones in feeding behaviour. Nutr Metabol 4:18
45. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33(Suppl):245-254
46. Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev 4:143-153
47. Choi JK, Kim YJ (2008) Epigenetic regulation and the variability of gene expression. Nat Genet 40:141-147
48. Reed AS, Unger EK, Olofsson LE, Piper ML, Myers MG Jr, Xu AW (2010) Functional role of suppressor of cytokine signaling 3 upregulation in hypothalamic leptin resistance and long-term energy homeostasis. Diabetes 59:894-906
49. Bjorbaek C, Elmquist JK, Frantz JD, Shoelson SE, Flier JS (1998) Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell 1:619-625
50. Thaler JP, Yi CX, Schur EA et al (2012) Obesity is associated with hypothalamic injury in rodents and humans. J Clin Investig 122:153-162