Induction of Gnrh mRNA expression by the ω-3 polyunsaturated fatty acid docosahexaenoic acid and the saturated fatty acid palmitate in a GnRH-synthesizing neuronal cell model, mHypoA-GnRH/GFP

Molecular and Cellular Endocrinology

Volumn 426, Issue , 2016, Pages 125-135

  Tran, Dean Q ^a   Ramos, Ernesto H ^a   Belsham, Denise D ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Cell biology; Free fatty acids; Gene expression; GnRH; Neuroendocrine; Signal transduction

Indexed keywords

DOCOSAHEXAENOIC ACID; G PROTEIN COUPLED RECEPTOR 120; GONADORELIN; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; OLEIC ACID; PALMITIC ACID; PALMITOLEIC ACID; PALMITOYL COENZYME A; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE C; TOLL LIKE RECEPTOR 4; G PROTEIN COUPLED RECEPTOR; LIPOPOLYSACCHARIDE; O3FAR1 PROTEIN, MOUSE; TLR4 PROTEIN, MOUSE;

ADULT; ANIMAL CELL; ARTICLE; BRAIN NERVE CELL; CELL CULTURE; CONTROLLED STUDY; ENZYME SYNTHESIS; GENE EXPRESSION; GENE EXPRESSION REGULATION; GNRH GENE; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; UPREGULATION; ANIMAL; BIOSYNTHESIS; DRUG EFFECTS; GENETIC TRANSCRIPTION; GENETICS; IMMUNOLOGY; MALE; METABOLISM; NERVE CELL;

ANIMALS; CELLS, CULTURED; DOCOSAHEXAENOIC ACIDS; GONADOTROPIN-RELEASING HORMONE; LIPOPOLYSACCHARIDES; MALE; MICE; NEURONS; PALMITIC ACID; RECEPTORS, G-PROTEIN-COUPLED; RNA, MESSENGER; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 4; TRANSCRIPTION, GENETIC; TRANSCRIPTIONAL ACTIVATION;

EID: 84959316368     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2016.02.019     Document Type: Article

References (65)

1. Akhtar W., de Jong J., Pindyurin Alexey V., Pagie L., Meuleman W., de Ridder J., Berns A., Wessels Lodewyk F.A., van Lohuizen M., van Steensel B. Chromatin position effects assayed by thousands of reporters integrated in parallel. Cell 2013, 154:914-927.
2. Belsham D.D., Mellon P.L. Transcription factors Oct-1 and C/EBPbeta (CCAAT/enhancer-binding protein-beta) are involved in the glutamate/nitric oxide/cyclic-guanosine 5'-monophosphate-mediated repression of mediated repression of gonadotropin-releasing hormone gene expression. Mol. Endocrinol. 2000, 14:212-228.
3. Belsham D.D., Cai F., Cui H., Smukler S.R., Salapatek A.M., Shkreta L. Generation of a phenotypic array of hypothalamic neuronal cell models to study complex neuroendocrine disorders. Endocrinology 2004, 145:393-400.
4. Blouet C., Schwartz G.J. Hypothalamic nutrient sensing in the control of energy homeostasis. Behav. Brain Res. 2010, 209:1-12.
5. Bradley R.L., Cheatham B. Regulation of ob gene expression and leptin secretion by insulin and dexamethasone in rat adipocytes. Diabetes 1999, 48:272-278.
6. Chan K.L., Pillon N.J., Sivaloganathan D.M., Costford S.R., Liu Z., Théret M., Chazaud B., Klip A. Palmitoleate reverses high fat-induced pro-inflammatory macrophage polarization via AMPK. J. Biol. Chem. 2015.
7. Cintra D.E., Ropelle E.R., Moraes J.C., Pauli J.R., Morari J., Souza C.T., Grimaldi R., Stahl M., Carvalheira J.B., Saad M.J., Velloso L.A. Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity. PLoS One 2012, 7:e30571.
8. Clark M.E., Mellon P.L. The POU homeodomain transcription factor Oct-1 is essential for activity of the gonadotropin-releasing hormone neuron-specific enhancer. Mol. Cell Biol. 1995, 15:6169-6177.
9. Clarke I.J., Pompolo S. Synthesis and secretion of GnRH. Anim. Reprod. Sci. 2005, 88:29-55.
10. Constantin S., Iremonger K.J., Herbison A.E. In vivo recordings of GnRH neuron firing reveal heterogeneity and dependence upon GABAA receptor signaling. J. Neurosci. 2013, 33:9394-9401.
11. Dalvi P.S., Erbiceanu F.D., Irwin D.M., Belsham D.D. Direct regulation of the proglucagon gene by insulin, leptin, and cAMP in embryonic versus adult hypothalamic neurons. Mol. Endocrinol. 2012, 26:1339-1355.
12. DeWire S.M., Ahn S., Lefkowitz R.J., Shenoy S.K. Beta-arrestins and cell signaling. Annu. Rev. Physiol. 2007, 69:483-510.
13. Erridge C., Samani N.J. Saturated fatty acids do not directly stimulate Toll-like receptor signaling. Arterioscler. Thromb. Vasc. Biol. 2009, 29:1944-1949.
14. Garrel G., Simon V., Denoyelle C., Cruciani-Guglielmacci C., Migrenne S., Counis R., Magnan C., Cohen-Tannoudji J. Unsaturated fatty acids stimulate LH secretion via novel PKCepsilon and -theta in gonadotrope cells and inhibit GnRH-induced LH release. Endocrinology 2011, 152:3905-3916.
15. Gill J., Sattar N. Ceramides: a new player in the inflammation-insulin resistance paradigm?. Diabetologia 2009, 52:2475-2477.
16. Gillespie J.M., Roy D., Cui H., Belsham D.D. Repression of gonadotropin-releasing hormone (GnRH) gene expression by melatonin may involve transcription factors COUP-TFI and C/EBP beta binding at the GnRH enhancer. Neuroendocrinology 2004, 79:63-72.
17. Givens M.L., Rave-Harel N., Goonewardena V.D., Kurotani R., Berdy S.E., Swan C.H., Rubenstein J.L., Robert B., Mellon P.L. Developmental regulation of gonadotropin-releasing hormone gene expression by the MSX and DLX homeodomain protein families. J. Biol. Chem. 2005, 280:19156-19165.
18. Gojska N.M., Friedman Z., Belsham D.D. Direct regulation of gonadotrophin-releasing hormone (GnRH) transcription by RF-amide-related peptide-3 and kisspeptin in a novel GnRH-secreting cell line, mHypoA-GnRH/GFP. J. Neuroendocrinol. 2014, 26:888-897.
19. Greco J.A., Oosterman J.E., Belsham D.D. Differential effects of omega-3 fatty acid docosahexaenoic acid and palmitate on the circadian transcriptional profile of clock genes in immortalized hypothalamic neurons. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2014, 307:R1049-R1060.
20. Gross D.S. Distribution of gonadotropin-releasing hormone in the mouse brain as revealed by immunohistochemistry. Endocrinology 1976, 98:1408-1417.
21. Hannun Y.A., Obeid L.M. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell Biol. 2008, 9:139-150.
22. Herde M.K., Geist K., Campbell R.E., Herbison A.E. Gonadotropin-releasing hormone neurons extend complex highly branched dendritic trees outside the blood-brain barrier. Endocrinology 2011, 152:3832-3841.
23. Hirasawa A., Tsumaya K., Awaji T., Katsuma S., Adachi T., Yamada M., Sugimoto Y., Miyazaki S., Tsujimoto G. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat. Med. 2005, 11:90-94.
24. Holland W.L., Brozinick J.T., Wang L.P., Hawkins E.D., Sargent K.M., Liu Y., Narra K., Hoehn K.L., Knotts T.A., Siesky A., Nelson D.H., Karathanasis S.K., Fontenot G.K., Birnbaum M.J., Summers S.A. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab. 2007, 5:167-179.
25. Huang S., Rutkowsky J.M., Snodgrass R.G., Ono-Moore K.D., Schneider D.A., Newman J.W., Adams S.H., Hwang D.H. Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. J. Lipid Res. 2012, 53:2002-2013.
26. Huang P.P., Iyer A.K., Mellon P.L. An enhancer-derived noncoding RNA in GnRH gene regulation, signaling and transcriptional control in endocrine systems 2013, pp. SAT-389-SAT-389.
27. Hussey Sophie E., Liang H., Costford Sheila R., Klip A., DeFronzo Ralph A., Sanchez-Avila A., Ely B., Musi N. TAK-242, a small-molecule inhibitor of Toll-like receptor 4 signalling, unveils similarities and differences in lipopolysaccharide- and lipidinduced inflammation and insulin resistance in muscle cells. Bioscience Reports 2013, 33:e00004.
28. Itoh Y., Kawamata Y., Harada M., Kobayashi M., Fujii R., Fukusumi S., Ogi K., Hosoya M., Tanaka Y., Uejima H., Tanaka H., Maruyama M., Satoh R., Okubo S., Kizawa H., Komatsu H., Matsumura F., Noguchi Y., Shinohara T., Hinuma S., Fujisawa Y., Fujino M. Free fatty acids regulate insulin secretion from pancreatic [beta] cells through GPR40. Nature 2003, 422:173-176.
29. Iyer A.K., Miller N.L., Yip K., Tran B.H., Mellon P.L. Enhancers of GnRH transcription embedded in an upstream gene use homeodomain proteins to specify hypothalamic expression. Mol. Endocrinol. 2010, 24:1949-1964.
30. Iyer A.K., Brayman M.J., Mellon P.L. Dynamic chromatin modifications control GnRH gene expression during neuronal differentiation and protein kinase C signal transduction. Mol. Endocrinol. 2011, 25:460-473.
31. Katsuma S., Hatae N., Yano T., Ruike Y., Kimura M., Hirasawa A., Tsujimoto G. Free fatty acids inhibit serum deprivation-induced apoptosis through GPR120 in a murine enteroendocrine cell line STC-1. J. Biol. Chem. 2005, 280:19507-19515.
32. Kenakin T. Biased agonism. F1000 Biol. Rep. 2009, 1:87.
33. Kim T.K., Hemberg M., Gray J.M., Costa A.M., Bear D.M., Wu J., Harmin D.A., Laptewicz M., Barbara-Haley K., Kuersten S., Markenscoff-Papadimitriou E., Kuhl D., Bito H., Worley P.F., Kreiman G., Greenberg M.E. Widespread transcription at neuronal activity-regulated enhancers. Nature 2010, 465:182-187.
34. Kwon B., Lee H.K., Querfurth H.W. Oleate prevents palmitate-induced mitochondrial dysfunction, insulin resistance and inflammatory signaling in neuronal cells. Biochim. Biophys. Acta 2014, 1843:1402-1413.
35. Lam M.T.Y., Li W., Rosenfeld M.G., Glass C.K. Enhancer RNAs and regulated transcriptional programs. Trends Biochem. Sci. 2014, 39:170-182.
36. Laulederkind S.J., Bielawska A., Raghow R., Hannun Y.A., Ballou L.R. Ceramide induces interleukin 6 gene expression in human fibroblasts. J. Exp. Med. 1995, 182:599-604.
37. Li W., Notani D., Ma Q., Tanasa B., Nunez E., Chen A.Y., Merkurjev D., Zhang J., Ohgi K., Song X., Oh S., Kim H.-S., Glass C.K., Rosenfeld M.G. Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature 2013, 498:516-520.
38. Ma L., Pei G. β-arrestin signaling and regulation of transcription. J. Cell Sci. 2007, 120:213-218.
39. McFadden S.A., Menchella J.A., Chalmers J.A., Centeno M.-L., Belsham D.D. Glucose responsiveness in a novel adult-derived GnRH cell line, mHypoA-GnRH/GFP: involvement of AMP-activated protein kinase. Mol. Cell. Endocrinol. 2013, 377:65-74.
40. Mellon P.L., Windle J.J., Goldsmith P.C., Padula C.A., Roberts J.L., Weiner R.I. Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron 1990, 5:1-10.
41. Migrenne S., Cruciani-Guglielmacci C., Kang L., Wang R., Rouch C., Lefèvre A.-L., Ktorza A., Routh V.H., Levin B.E., Magnan C. Fatty acid signaling in the hypothalamus and the neural control of insulin secretion. Diabetes 2006, 55:S139-S144.
42. Milanski M., Degasperi G., Coope A., Morari J., Denis R., Cintra D.E., Tsukumo D.M., Anhe G., Amaral M.E., Takahashi H.K., Curi R., Oliveira H.C., Carvalheira J.B., Bordin S., Saad M.J., Velloso L.A. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J. Neurosci. 2009, 29:359-370.
43. Mobraten K., Haug T.M., Kleiveland C.R., Lea T. Omega-3 and omega-6 PUFAs induce the same GPR120-mediated signalling events, but with different kinetics and intensity in Caco-2 cells. Lipids Health Dis. 2013, 12. 101-101.
44. Morad S.A., Cabot M.C. Ceramide-orchestrated signalling in cancer cells. Nat. Rev. Cancer 2013, 13:51-65.
45. Natoli G., Andrau J.-C. Noncoding transcription at enhancers: general principles and functional models. Annu. Rev. Genet. 2012, 46:1-19.
46. Nelson S.B., Eraly S.A., Mellon P.L. The GnRH promoter: target of transcription factors, hormones, and signaling pathways. Mol. Cell. Endocrinol. 1998, 140:151-155.
47. Nelson S.B., Lawson M.A., Kelley C.G., Mellon P.L. Neuron-specific expression of the rat gonadotropin-releasing hormone gene is conferred by interactions of a defined promoter element with the enhancer in GT1-7 cells. Mol. Endocrinol. 2000, 14:1509-1522.
48. Oh D.Y., Talukdar S., Bae E.J., Imamura T., Morinaga H., Fan W., Li P., Lu W.J., Watkins S.M., Olefsky J.M. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010, 142:687-698.
49. Pennacchio L.A., Bickmore W., Dean A., Nobrega M.A., Bejerano G. Enhancers: five essential questions. Nat. Rev. Genet. 2013, 14:288-295.
50. Pu J., Peng G., Li L., Na H., Liu Y., Liu P. Palmitic acid acutely stimulates glucose uptake via activation of Akt and ERK1/2 in skeletal muscle cells. J. Lipid Res. 2011, 52:1319-1327.
51. Radovick S., Wray S., Lee E., Nicols D.K., Nakayama Y., Weintraub B.D., Westphal H., Cutler G.B., Wondisford F.E. Migratory arrest of gonadotropin-releasing hormone neurons in transgenic mice. Proc. Natl. Acad. Sci. 1991, 88:3402-3406.
52. Rose M.L., Germolec D.R., Schoonhoven R., Thurman R.G. Kupffer cells are causally responsible for the mitogenic effect of peroxisome proliferators. Carcinogenesis 1997, 18:1453-1456.
53. Schilling J.D., Machkovech H.M., He L., Sidhu R., Fujiwara H., Weber K., Ory D.S., Schaffer J.E. Palmitate and lipopolysaccharide trigger synergistic ceramide production in primary macrophages. J. Biol. Chem. 2013, 288:2923-2932.
54. Sharma S., Morinaga H., Hwang V., Fan W., Fernandez M.O., Varki N., Olefsky J.M., Webster N.J. Free fatty acids induce Lhb mRNA but suppress Fshb mRNA in pituitary LbetaT2 gonadotropes and diet-induced obesity reduces FSH levels in male mice and disrupts the proestrous LH/FSH surge in female mice. Endocrinology 2013, 154:2188-2199.
55. Shi H., Kokoeva M., Inouye K., Tzameli I., Yin H., Flier J. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Investig. 2006, 116:3015-3025.
56. Sun S.C., Ganchi P.A., Ballard D.W., Greene W.C. NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway. Science 1993, 259:1912-1915.
57. Talukdar S., Olefsky J.M., Osborn O. Targeting GPR120 and other fatty acid sensing GPCRs ameliorates insulin resistance and inflammatory diseases. Trends Pharmacol. Sci. 2011, 32:543-550.
58. Tang Q., Mazur M., Mellon P.L. The protein kinase C pathway acts through multiple transcription factors to repress gonadotropin-releasing hormone gene expression in hypothalamic GT1-7 neuronal cells. Mol. Endocrinol. 2005, 19:2769-2779.
59. Ten R.M., Paya C.V., Israel N., Le Bail O., Mattei M.G., Virelizier J.L., Kourilsky P., Israel A. The characterization of the promoter of the gene encoding the p50 subunit of NF-kappa B indicates that it participates in its own regulation. Embo J. 1992, 11:195-203.
60. Vanholder T., Leroy J.L., Soom A.V., Opsomer G., Maes D., Coryn M., de Kruif A. Effect of non-esterified fatty acids on bovine granulosa cell steroidogenesis and proliferation in vitro. Anim. Reprod. Sci. 2005, 87:33-44.
61. Wellhauser L., Belsham D.D. Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons. J. Neuroinflammation 2014, 11:60.
62. Whyte D.B., Lawson M.A., Belsham D.D., Eraly S.A., Bond C.T., Adelman J.P., Mellon P.L. A neuron-specific enhancer targets expression of the gonadotropin-releasing hormone gene to hypothalamic neurosecretory neurons. Mol. Endocrinol. 1995, 9:467-477.
63. Yamashita A., Hayashi Y., Nemoto-Sasaki Y., Ito M., Oka S., Tanikawa T., Waku K., Sugiura T. Acyltransferases and transacylases that determine the fatty acid composition of glycerolipids and the metabolism of bioactive lipid mediators in mammalian cells and model organisms. Prog. Lipid Res. 2014, 53:18-81.
64. Yan L., Bai X.L., Fang Z.F., Che L.Q., Xu S.Y., Wu D. Effect of different dietary omega-3/omega-6 fatty acid ratios on reproduction in male rats. Lipids Health Dis. 2013, 12:33.
65. Zhang G., Li J., Purkayastha S., Tang Y., Zhang H., Yin Y., Li B., Liu G., Cai D. Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature 2013, 497:211-216.