Hypothalamic ceramide levels regulated by cpt1c mediate the orexigenic effect of ghrelin

Diabetes

Volumn 62, Issue 7, 2013, Pages 2329-2337

  Ramírez, Sara ^a,b   Martins, Luís ^b,c   Jacas, Jordi ^a,b   Carrasco, Patricia ^a,b   Pozo, Macarena ^a,b   Clotet, Josep ^a   Serra, Dolors ^b,d   Hegardt, Fausto G ^b,d   Diéguez, Carlos ^b,c   López, Miguel ^b,c   Casals, Núria ^a,b  

^a UNIVERSITAT INTERNACIONAL DE CATALUNYA   (Spain)

^b Instituto de Salud Carlos III   (Spain)

^c UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

^d UNIVERSITY OF BARCELONA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

AGOUTI RELATED PROTEIN; CARNITINE PALMITOYLTRANSFERASE 1C; CARNITINE PALMITOYLTRANSFERASE I; CERAMIDE; FORKHEAD BOX O1; GHRELIN; NEUROPEPTIDE; THERMOZYMOCIDIN; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; CARNITINE PALMITOYLTRANSFERASE; NEUROPEPTIDE Y;

ADULT; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG EFFECT; FOOD INTAKE; HYPOTHALAMUS; INTRACEREBROVENTRICULAR DRUG ADMINISTRATION; LIPID METABOLISM; LIPOGENESIS; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; UPREGULATION; ANIMAL; EATING; GENETICS; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

AGOUTI-RELATED PROTEIN; ANIMALS; CARNITINE O-PALMITOYLTRANSFERASE; CERAMIDES; EATING; GHRELIN; HYPOTHALAMUS; MALE; MICE; MICE, KNOCKOUT; NEUROPEPTIDE Y; SIGNAL TRANSDUCTION;

EID: 84878778837     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db12-1451     Document Type: Article

References (35)

1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656-660
2. Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000;407:908-913
3. Anderson KA, Ribar TJ, Lin F, et al. Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab 2008;7:377-388
4. López M, Lage R, Saha AK, et al. Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab 2008;7:389-399
5. Andrews ZB, Liu ZW, Walllingford N, et al. UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals. Nature 2008;454:846-851
6. Dietrich MO, Antunes C, Geliang G, et al. Agrp neurons mediate Sirt1's action on the melanocortin system and energy balance: roles for Sirt1 in neuronal firing and synaptic plasticity. J Neurosci 2010;30:11815-11825
7. Velásquez DA, Martínez G, Romero A, et al. The central Sirtuin 1/p53 pathway is essential for the orexigenic action of ghrelin. Diabetes 2011;60: 1177-1185
8. Sakkou M, Wiedmer P, Anlag K, et al. A role for brain-specific homeobox factor Bsx in the control of hyperphagia and locomotory behavior. Cell Metab 2007;5:450-463
9. Sierra AY, Gratacós E, Carrasco P, et al. CPT1c is localized in endoplasmic reticulum of neurons and has carnitine palmitoyltransferase activity. J Biol Chem 2008;283:6878-6885
10. Price N, van der Leij F, Jackson V, et al. A novel brain-expressed protein related to carnitine palmitoyltransferase I. Genomics 2002;80:433-442
11. Wolfgang MJ, Kurama T, Dai Y, et al. The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis. Proc Natl Acad Sci USA 2006;103:7282-7287
12. Wolfgang MJ, Lane MD. The role of hypothalamic malonyl-CoA in energy homeostasis. J Biol Chem 2006;281:37265-37269
13. Wolfgang MJ, Lane MD. Hypothalamic malonyl-CoA and CPT1c in the treatment of obesity. FEBS J 2011;278:552-558
14. Gao XF, Chen W, Kong XP, et al. Enhanced susceptibility of Cpt1c knockout mice to glucose intolerance induced by a high-fat diet involves elevated hepatic gluconeogenesis and decreased skeletal muscle glucose uptake. Diabetologia 2009;52:912-920
15. Gao S, Zhu G, Gao X, et al. Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding. Proc Natl Acad Sci USA 2011;108:9691-9696
16. Sun Y, Wang P, Zheng H, Smith RG. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci USA 2004;101:4679-4684
17. Merrill AH Jr, Sullards MC, Allegood JC, Kelly S, Wang E. Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods 2005;36:207-224
18. López M, Lelliott CJ, Tovar S, et al. Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA. Diabetes 2006;55: 1327-1336
19. López M, Varela L, Vázquez MJ, et al. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med 2010; 16:1001-1008
20. Whittle AJ, Carobbio S, Martins L, et al. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell 2012;149:871-885
21. Martínez de Morentin PB, Whittle AJ, Fernø J, et al. Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase. Diabetes 2012;61:807-817
22. Carrasco P, Sahún I, McDonald J, et al. Ceramide levels regulated by carnitine palmitoyltransferase 1C control dendritic spine maturation and cognition. J Biol Chem 2012;287:21224-21232
23. Ben-David O, Futerman AH. The role of the ceramide acyl chain length in neurodegeneration: involvement of ceramide synthases. Neuromolecular Med 2010;12:341-350
24. Hanada K, Nishijima M, Fujita T, Kobayashi S. Specificity of inhibitors of serine palmitoyltransferase (SPT), a key enzyme in sphingolipid biosynthesis, in intact cells. A novel evaluation system using an SPT-defective mammalian cell mutant. Biochem Pharmacol 2000;59:1211-1216
25. Mitoma J, Ito M, Furuya S, Hirabayashi Y. Bipotential roles of ceramide in the growth of hippocampal neurons: promotion of cell survival and dendritic outgrowth in dose- and developmental stage-dependent manners. J Neurosci Res 1998;51:712-722
26. Zigman JM, Elmquist JK. Minireview: From anorexia to obesity - the yin and yang of body weight control. Endocrinology 2003;144:3749-3756
27. Nogueiras R, Tschöp M. Biomedicine. Separation of conjoined hormones yields appetite rivals. Science 2005;310:985-986
28. Hannun YA, Obeid LM. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 2008;9:139-150
29. Lelliott C, Vidal-Puig AJ. Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation. Int J Obes Relat Metab Disord 2004;28 (Suppl. 4):S22-S28
30. Virtue S, Vidal-Puig A. It's not how fat you are, it's what you do with it that counts. PLoS Biol 2008;6:e237
31. Martínez de Morentin PB, Varela L, Fernø J, Nogueiras R, Diéguez C, López M. Hypothalamic lipotoxicity and the metabolic syndrome. Biochim Biophys Acta 2010;1801:350-361
32. Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKbeta/ NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 2008;135:61-73
33. Hosoi T, Sasaki M, Miyahara T, et al. Endoplasmic reticulum stress induces leptin resistance. Mol Pharmacol 2008;74:1610-1619
34. Ozcan L, Ergin AS, Lu A, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab 2009;9:35-51
35. Won JC, Jang PG, Namkoong C, et al. Central administration of an endoplasmic reticulum stress inducer inhibits the anorexigenic effects of leptin and insulin. Obesity (Silver Spring) 2009;17:1861-1865