Interleukin-6 regulates the expression of hypothalamic neuropeptides involved in body weight in a gender-dependent way

Journal of Neuroendocrinology

Volumn 23, Issue 8, 2011, Pages 675-686

  Senaris R M ^a   Trujillo, M L ^a   Navia, B ^a   Comes, G ^b   Ferrer, B ^b   Giralt, M ^b   Hidalgo, J ^b  

^a UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

^b INSTITUT DE NEUROCIÈNCIES   (Spain)

Author keywords

Body weight; Gender; Hypothalamus; Interleukin 6; Neuropeptides

Indexed keywords

AGOUTI RELATED PEPTIDE; CORTICOTROPIN RELEASING FACTOR; GLIAL FIBRILLARY ACIDIC PROTEIN; GLUCOSE; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; MELANIN CONCENTRATING HORMONE; MESSENGER RNA; NEUROPEPTIDE; NEUROPEPTIDE Y; PREPROOREXIN; PROOPIOMELANOCORTIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BODY FAT; CEREBELLUM; CONTROLLED STUDY; DIET RESTRICTION; FEMALE; GENE OVEREXPRESSION; GLUCOSE BLOOD LEVEL; HOMEOSTASIS; HYPOTHALAMUS; IMMUNOASSAY; IN SITU HYBRIDIZATION; LIPID DIET; LIVER; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; REGULATORY MECHANISM; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA EXTRACTION; SPLEEN; TRANSGENIC MOUSE; WEIGHT CONTROL;

AGOUTI-RELATED PROTEIN; ANIMALS; BLOOD GLUCOSE; BODY WEIGHT; CORTICOTROPIN-RELEASING HORMONE; DIET, HIGH-FAT; ENERGY METABOLISM; FEMALE; FOOD DEPRIVATION; HOMEOSTASIS; HYPOTHALAMIC HORMONES; HYPOTHALAMUS; INTERLEUKIN-6; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MALE; MELANINS; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; NEUROPEPTIDE Y; NEUROPEPTIDES; PITUITARY HORMONES; PRO-OPIOMELANOCORTIN; SEX CHARACTERISTICS;

EID: 79960259726     PISSN: 09538194     EISSN: 13652826     Source Type: Journal    
DOI: 10.1111/j.1365-2826.2011.02158.x     Document Type: Article

References (55)

1. Bauer S, Kerr BJ, Patterson PH. The neuropoietic cytokine family in development, plasticity, disease and injury. Nat Rev Neurosci 2007; 8: 221-232.
2. Mohamed-Ali V, Flower L, Sethi J, Hotamisligil G, Gray R, Humphries SE, York DA, Pinkney J. Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies. J Clin Endocrinol Metab 2001; 86: 5864-5869.
3. Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A, Tyson K, Chrousos GP. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 1997; 82: 1313-1316.
4. Pedersen BK, Steensberg A, Schjerling P. Muscle-derived interleukin-6: possible biological effects. J Physiol 2001; 536: 329-337.
5. Jonsdottir IH, Schjerling P, Ostrowski K, Asp S, Richter EA, Pedersen BK. Muscle contractions induce interleukin-6 mRNA production in rat skeletal muscles. J Physiol 2000; 528: 157-163.
6. Schöbitz B, de Kloet ER, Sutanto W, Holsboer F. Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain. Eur J Neurosci 1993; 5: 1426-1435.
7. Shizuya K, Komori T, Fujiwara R, Miyahara S, Ohmori M, Nomura J. The expressions of mRNAs for interleukin-6 (IL-6) and the IL-6 receptor (IL-6R) in the rat hypothalamus and midbrain during restraint stress. Life Sci 1998; 62: 2315-2320.
8. Aschner M. Immune and inflammatory responses in the CNS: modulation by astrocytes. Toxicology 1998; 102-103: 283-287.
9. Van Wagoner NJ, Oh JW, Repovic P, Benveniste EN. Interleukin-6 (IL-6) production by astrocytes: autocrine regulation by IL-6 and the soluble IL-6 receptor. J Neurosci 1999; 19: 5236-5244.
10. Spangelo BL, Gorospe WC. Role of the cytokines in the neuroendocrine-immune system axis. Front Neuroendocrinol 1995; 16: 1-22.
11. Gadient RA, Otten UH. Interleukin-6 (IL-6): a molecule with both beneficial and destructive potentials. Prog Neurobiol 1997; 52: 379-390.
12. Juttler E, Tarabin V, Schwaninger M. Interleukin-6 (IL-6): a possible neuromodulator induced by neuronal activity. Neuroscientist 2002; 8: 268-275.
13. Murphy PG, Ramer MS, Borthwick L, Gauldie J, Richardson PM, Bisby MA. Endogenous interleukin-6 contributes to hypersensitivity to cutaneous stimuli and changes in neuropeptides associated with chronic nerve constriction in mice. Eur J Neurosci 1999; 11: 2243-2253.
14. Armario A, Hernández J, Bluethmann H, Hidalgo J. IL-6 deficiency leads to increased emotionality in mice: evidence in transgenic mice carrying a null mutation for IL-6. J Neuroimmunol 1998; 92: 160-169.
15. Chai Z, Gatti S, Toniatti C, Poli V, Bartfai T. Interleukin (IL)-6 gene expression in the central nervous system is necessary for fever response to lipopolysaccharide or IL-1 beta: a study on IL-6-deficient mice. J Exp Med 1996; 183: 311-316.
16. Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 2002; 8: 75-79.
17. Wallenius K, Wallenius V, Sunter D, Dickson SL, Jansson JO. Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem Biophys Res Commun 2002; 293: 560-565.
18. Benrick A, Schéle E, Pinnock SB, Wernstedt-Asterholm I, Dickson SL, Karlsson-Lindahl L, Jansson JO. Interleukin-6 gene knockout influences energy balance regulating peptides in the hypothalamic paraventricular and supraoptic nuclei. J Neuroendocrinol 2009; 21: 620-628.
19. Ropelle ER, Flores MB, Cintra DE, Rocha GZ, Pauli JR, Morari J, de Souza CT, Moraes JC, Prada PO, Guadagnini D, Marin RM, Oliveira AG, Augusto TM, Carvalho HF, Velloso LA, Saad MJA, Carvalheira JBC. IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKb and ER stress inhibition. PLoS Biol 2010; 8: pii: e1000465.
20. Saper CB, Chou TC, Elmquist JK. The need to feed: homeostatic and hedonic control of eating. Neuron 2002; 36: 199-211.
21. Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr Rev 1999; 20: 68-100.
22. Millington GWM. The role of proopiomelanocortin (POMC) neurones in feeding behaviour. Nutr Metab (Lond) 2007; 4: 18.
23. Vianna CR, Coppari R. A treasure trove of hypothalamic neurocircuitries governing body weight homeostasis. Endocrinology 2011; 152: 11-18.
24. Brown MR, Fisher LA, Spiess J, Rivier C, Rivier J, Vale W. Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology 1982; 111: 928-931.
25. Hidalgo J, Florit S, Giralt M, Ferrer B, Keller C, Pilegaard H. Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat. Brain Behav Immun 2010; 24: 119-126.
26. Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MBA, Mucke L. Neurologic disease in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci USA 1993; 90: 10061-10065.
27. López M, Seoane L, Tovar S, García MC, Nogueiras R, Dieguez C, Señarís R. A possible role of neuropeptide Y, agouti-related protein and leptin receptor isoforms in hypothalamic programming by perinatal feeding in the rat. Diabetologia 2005; 48: 140-148.
28. García MC, López M, Gualillo O, Seoane LM, Diéguez C, Señarís RM. Hypothalamic levels of NPY, MCH, and prepro-orexin mRNA during pregnancy and lactation in the rat: role of prolactin. FASEB J 2003; 17: 1392-1400.
29. Trujillo ML, Spuch C, Carro E, Señarís R. Hyperphagia and central mechanisms for leptin resistance during pregnancy. Endocrinology 2011; 152: 1355-1365.
30. Paxinos G, Franklin KBJ. The Mouse Brain in Stereotaxic Coordinates. San Diego, CA: Academic Press, 2003.
31. Campbell IL. Structural and functional impact of the transgenic expression of cytokines in the CNS. Ann NY Acad Sci 1998; 840: 83-96.
32. Li G, Klein RL, Matheny M, King MA, Meyer EM, Scarpace PJ. Induction of uncoupling protein 1 by central interleukin-6 gene delivery is dependent on sympathetic innervation of brown adipose tissue and underlies one mechanism of body weight reduction in rats. Neuroscience 2002; 115: 879-889.
33. Quintana A, Muller M, Frausto RF, Ramos R, Getts DR, Sanz E, Hofer MJ, Krauthausen M, King NJC, Hidalgo J, Campbel IL. Site-specific production of IL-6 in the central nervous system retargets and enhances the inflammatory response in experimental autoimmune encephalomyelitis. J Immunol 2009; 183: 2079-2088.
34. Hernández J, Molinero A, Campbell IL, hidalgo J. Transgenic expression of interleukin-6 in the central nervous system regulates brain metalothionein-I and -III expression in mice. Mol Brain Res 1997; 48: 125-131.
35. Votruba SB, Jensen MD. Regional fat deposition as a factor in FFA metabolism. Annu Rev Nutr 2007; 27: 149-163.
36. Liu H, Liu K, Bodenner DL. Estrogen receptor inhibits interleukin-6 gene expression by disruption of nuclear factor [kappa]B transactivation. Cytokine 2005; 31: 251-257.
37. Stein B, Yang MX. Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta. Mol Cell Biol 1995; 15: 4971-4979.
38. Naugler WE, Sakurai T, Kim S, Maeda S, Kim KH, Elsharkawy AM, Karin M. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 2007; 317: 121-124.
39. Gao Q, Mezei G, Nie Y, Rao Y, Choi CS, Bechmann I, Leranth C, Toran-Allerand D, Priest CA, Roberts JL, Gao XB, Mobbs C, Shulman GI, Diano S, Horvath TL. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nat Med 2007; 13: 89-94.
40. Young LJ, Muns S, Wang Z. Oxytocin receptor gene expression in rat brain during pregnancy: interaction of estrogen and interleukin-6. J Neuroendocrinol 1997; 9: 859-865.
41. Gao Q, Horvath TL. Neurobiology of feeding and energy expenditure. Annu Rev Neurosci 2007; 30: 367-398.
42. Levine AS, Jewett DC, Cleary JP, Kotz CM, Billington CJ. Our journey with neuropeptide Y: effects on ingestive behaviors and energy expenditure. Peptides 2004; 25: 505-510.
43. Coll AP, Farooqi IS, Challis BG, Yeo GSH, O'Rahilly S. Proopiomelanocortin and energy balance: insights from human and murine genetics. J Clin Endocrinol Metab 2004; 89: 2557-2562.
44. Small CJ, Liu YL, Stanley SA, Connoley IP, Kennedy A, Stock MJ, Bloom SR. Chronic CNS administration of Agouti-related protein (AgRP) reduces energy expenditure. Int J Obes Relat Metab Disord 2003; 27: 530-533.
45. Wortley KE, Anderson KD, Yasenchak J, Murphy A, Valenzuela D, Diano S, Yancopoulos GD, Wiegand SJ, Sleeman MW. Agouti-related protein-deficient mice display an age-related lean phenotype. Cell Metab 2005; 2: 421-427.
46. Makimura H, Mizuno TM, Mastaitis JW, Agami R, Mobbs CV. Reducing hypothalamic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake. BMC Neurosci 2002; 7: 18.
47. Wernstedt I, Edgley A, Berndtsson A, Fäldt J, Bergström G, Wallenius V, Jansson JO. Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice. Am J Physiol Regul Integr Comp Physiol 2006; 291: R551-R557.
48. Faldt J, Wernsted I, Fitzgerald SM, Wallenius K, Bergstrom G, Jansson JO. Reduced exercise endurance in interleukin-6-deficient mice. Endocrinology 2004; 145: 2680-2686.
49. Sadagurski M, Norquay L, Farhang J, D'Aquino K, Copps K, White MF. Human IL6 enhances leptin action in mice. Diabetologia 2010; 53: 525-535.
50. Ernst M, Jenkins BJ. Acquiring signalling specificity from the cytokine receptor gp130. Trends Genet 2004; 20: 23-32.
51. Ziotopoulou M, Erani DM, Hileman SM, Bjørbæk C, Mantzoros CS. Unlike leptin, ciliary neurotrophic factor does not reverse the starvation-induced changes of serum corticosterone and hypothalamic neuropeptide levels but induces expression of hypothalamic inhibitors of leptin signaling. Diabetes 2000; 49: 1890-1896.
52. Lambert PD, Anderson KD, Sleeman MW, Wong V, Tan J, Hijarunguru A, Corcoran TL, Murray JD, Thabet KE, Yancopoulos GD, Wiegand SJ. Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity. PNAS 2001; 98: 4652-4657.
53. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS. Role of leptin in the neuroendocrine response to fasting. Nature 1996; 382: 250-252.
54. Enriori PJ, Evans AE, Sinnayah P, Jobst EE, Tonelli-Lemos L, Billes SK, Glavas MM, Grayson BE, Perello M, Nillni EA, Grove KL, Cowley MA. Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Cell Metab 2007; 5: 181-194.
55. Takahashi N, Patel HR, Qi Y, Dushay J, Ahima RS. Divergent effects of leptin in mice susceptible or resistant to obesity. Horm Metab Res 2002; 34: 691-697.