Orexin-A represses satiety-inducing POMC neurons and contributes to obesity via stimulation of endocannabinoid signaling

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 17, 2016, Pages 4759-4764

  Morello, Giovanna ^a,b   Imperatore, Roberta ^a   Palomba, Letizia ^c   Finelli, Carmine ^d   Labruna, Giuseppe ^e   Pasanisi, Fabrizio ^d   Sacchetti, Lucia ^f   Buono, Lorena ^a,g   Piscitelli, Fabiana ^a   Orlando, Pierangelo ^h   Di Marzo, Vincenzo ^a   Cristino, Luigia ^a  

^a CNR   (Italy)

^b UNIVERSITY OF VERONA   (Italy)

^c UNIVERSITY OF URBINO   (Italy)

^d FEDERICO II UNIVERSITY HOSPITAL   (Italy)

^e SDN IRCCS Institute of Diagnostic and Nuclear Research   (Italy)

^f Centro di Ingegneria Genetica Advanced Biotechnology   (Italy)

^g UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

^h INSTITUTE OF PROTEIN BIOCHEMISTRY   (Italy)

Author keywords

2 arachidonoylglycerol; Cannabinoid type 1 receptor; Hypocretin 1; Hypothalamus; melanocyte stimulating hormone

Indexed keywords

2 ARACHIDONOYLGLYCEROL; ALANINE AMINOTRANSFERASE; ALPHA INTERMEDIN; CANNABINOID 1 RECEPTOR; ENDOCANNABINOID; GAMMA GLUTAMYLTRANSFERASE; LEPTIN; MITOGEN ACTIVATED PROTEIN KINASE 1; OREXIN 1 RECEPTOR; OREXIN A; PROOPIOMELANOCORTIN; STAT3 PROTEIN; OREXIN;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; APPETITE; ARCUATE NUCLEUS; ARTICLE; BRAIN NERVE CELL; CEREBROSPINAL FLUID; CONTROLLED STUDY; DOWN REGULATION; ENZYME PHOSPHORYLATION; FATTY LIVER; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; HORMONE RELEASE; HUMAN; HUMAN CELL; HYPERPHAGIA; MALE; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; SATIETY; SIGNAL TRANSDUCTION; STEATOSIS; ANIMAL; ANTERIOR HYPOTHALAMIC NUCLEUS; C57BL MOUSE; CELL CULTURE; METABOLISM; NERVE CELL; NERVE CELL INHIBITION; PATHOLOGY; SATIETY RESPONSE; UPREGULATION;

ADULT; ALPHA-MSH; ANIMALS; ANTERIOR HYPOTHALAMIC NUCLEUS; CELLS, CULTURED; ENDOCANNABINOIDS; HUMANS; MALE; MICE; MICE, INBRED C57BL; NEURAL INHIBITION; NEURONS; OBESITY; OREXINS; PRO-OPIOMELANOCORTIN; SATIETY RESPONSE; SIGNAL TRANSDUCTION; UP-REGULATION;

EID: 84964769123     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1521304113     Document Type: Article

References (40)

1. Flores A, Maldonado R, Berrendero F (2013) Cannabinoid-hypocretin cross-talk in the central nervous system: What we know so far. Front Neurosci 7:256.
2. Di Marzo V, et al. (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410(6830):822-825.
3. Di Marzo V (2011) Endocannabinoids: An appetite for fat. Proc Natl Acad Sci USA 108(31):12567-12568.
4. Sakurai T (2014) Roles of orexins in the regulation of body weight homeostasis. Obes Res Clin Pract 8(5):e414-e420.
5. Turunen PM, Jäntti MH, Kukkonen JP (2012) OX1 orexin/hypocretin receptor signaling through arachidonic acid and endocannabinoid release. Mol Pharmacol 82(2): 156-167.
6. Ho J, Cox JM, Wagner EJ (2007) Cannabinoid-induced hyperphagia: Correlation with inhibition of proopiomelanocortin neurons? Physiol Behav 92(3):507-519.
7. Cristino L, et al. (2016) Orexin-A and endocannabinoid activation of the descending antinociceptive pathway underlies altered pain perception in leptin signaling deficiency. Neuropsychopharmacology 41(2):508-520.
8. Schwartz MW, Woods SC, Porte D, Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404(6778):661-671.
9. Cone RD (2005) Anatomy and regulation of the central melanocortin system. Nat Neurosci 8(5):571-578.
10. Elias CF, et al. (1998) Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J Comp Neurol 402(4):442-459.
11. Yaswen L, Diehl N, Brennan MB, Hochgeschwender U (1999) Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 5(9):1066-1070.
12. Balthasar N, et al. (2004) Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42(6):983-991.
13. Cone RD (2000) Haploinsufficiency of the melanocortin-4 receptor: Part of a thrifty genotype? J Clin Invest 106(2):185-187.
14. Ma X, Zubcevic L, Brüning JC, Ashcroft FM, Burdakov D (2007) Electrical inhibition of identified anorexigenic POMC neurons by orexin/hypocretin. J Neurosci 27(7): 1529-1533.
15. Chemelli RM, et al. (1999) Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation. Cell 98(4):437-451.
16. Kiyashchenko LI, et al. (2002) Release of hypocretin (orexin) during waking and sleep states. J Neurosci 22(13):5282-5286.
17. López M, et al. (2007) Orexin expression is regulated by alpha-melanocyte-stimulating hormone. J Neuroendocrinol 19(9):703-707.
18. Koch M, et al. (2015) Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature 519(7541):45-50.
19. Crespo I, Gómez de Heras R, Rodríguez de Fonseca F, Navarro M (2008) Pretreatment with subeffective doses of rimonabant attenuates orexigenic actions of orexin A-hypocretin 1. Neuropharmacology 54(1):219-225.
20. Cristino L, et al. (2013) Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons. Proc Natl Acad Sci USA 110(24):E2229-E2238.
21. Hentges ST (2007) Synaptic regulation of proopiomelanocortin neurons can occur distal to the arcuate nucleus. J Neurophysiol 97(5):3298-3304.
22. Bénard G, et al. (2012) Mitochondrial CB1 receptors regulate neuronal energy metabolism. Nat Neurosci 15(4):558-564.
23. Bouaboula M, et al. (1995) Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem J 312(Pt 2):637-641.
24. Ammoun S, Lindholm D, Wootz H, Akerman KE, Kukkonen JP (2006) G-protein-coupled OX1 orexin/hcrtr-1 hypocretin receptors induce caspase-dependent and-independent cell death through p38 mitogen-/stress-activated protein kinase. J Biol Chem 281(2):834-842.
25. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89(1): 309-380.
26. Chen Z, et al. (2001) MAP kinases. Chem Rev 101(8):2449-2476.
27. Kyosseva SV (2004) Mitogen-activated protein kinase signaling. Int Rev Neurobiol 59:201-220.
28. El-Sedeek MSh, Korish AA, Deef MM (2010) Plasma orexin-A levels in postmenopausal women: Possible interaction with estrogen and correlation with cardiovascular risk status. BJOG 117(4):488-492.
29. Messina G, et al. (2013) Hormonal changes in menopause and orexin-A action. Obstet Gynecol Int 2013:209812.
30. Burke LK, et al. (2016) Sex difference in physical activity, energy expenditure and obesity driven by a subpopulation of hypothalamic POMC neurons. Mol Metab 5(3): 245-252.
31. Baranowska B, Woli-nska-Witort E, Marty-nska L, Chmielowska M, Baranowska-Bik A (2005) Plasma orexin A, orexin B, leptin, neuropeptide Y (NPY) and insulin in obese women. Neuroendocrinol Lett 26(4):293-296.
32. Tam J, et al. (2012) Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance. Cell Metab 16(2):167-179.
33. Bellocchio L, et al. (2010) Bimodal control of stimulated food intake by the endocannabinoid system. Nat Neurosci 13(3):281-283.
34. Monteleone P, et al. (2005) Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa. Neuropsychopharmacology 30(6):1216-1221.
35. Nicholson J, et al. (2015) Leptin levels are negatively correlated with 2-arachidonoylglycerol in the cerebrospinal fluid of patients with osteoarthritis. PLoS One 10(4):e0123132.
36. Yoshida Y, et al. (2001) Fluctuation of extracellular hypocretin-1 (orexin A) levels in the rat in relation to the light-dark cycle and sleep-wake activities. Eur J Neurosci 14(7):1075-1081.
37. Fujiki N, et al. (2001) Changes in CSF hypocretin-1 (orexin A) levels in rats across 24 hours and in response to food deprivation. Neuroreport 12(5):993-997.
38. Tabuchi S, et al. (2014) Conditional ablation of orexin/hypocretin neurons: A new mouse model for the study of narcolepsy and orexin system function. J Neurosci 34(19):6495-6509.
39. Nobunaga M, et al. (2014) High fat diet induces specific pathological changes in hypothalamic orexin neurons in mice. Neurochem Int 78:61-66.
40. Kälin S, et al. (2015) Hypothalamic innate immune reaction in obesity. Nat Rev Endocrinol 11(6):339-351.