Loss of NSCL-2 in gonadotropin releasing hormone neurons leads to reduction of pro-opiomelanocortin neurons in specific hypothalamic nuclei and causes visceral obesity

Journal of Neuroscience

Volumn 33, Issue 25, 2013, Pages 10459-10470

  Schmid, Thomas ^a   Günther, Stefan ^a   Mendler, Luca ^b   Braun, Thomas ^a  

^a MAX PLANCK INSTITUTE FOR HEART AND LUNG RESEARCH   (Germany)

^b UNIVERSITY OF SZEGED   (Hungary)

Author keywords

[No Author keywords available]

Indexed keywords

ESTRADIOL; GONADORELIN; PROOPIOMELANOCORTIN;

ABDOMINAL OBESITY; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; ELISA KIT; FAT MASS; FEMALE; GENE; GENE INACTIVATION; GENE LOSS; HYPOGONADOTROPIC HYPOGONADISM; HYPOTHALAMUS NUCLEUS; IMMUNOFLUORESCENCE TEST; MOUSE; MUTANT; NERVE CELL; NONHUMAN; NSCL 2 GENE; OVARIECTOMY; POSTERIOR HYPOTHALAMUS; PRIORITY JOURNAL; SENESCENCE; WESTERN BLOTTING;

ADIPOSE TISSUE; ADRENOCORTICOTROPIC HORMONE; ANIMALS; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; BLOTTING, WESTERN; CELL DIVISION; ESTRADIOL; FEMALE; GONADOTROPIN-RELEASING HORMONE; HOMEOSTASIS; HYPOTHALAMUS; HYPOTHALAMUS, POSTERIOR; INFERTILITY; MICE; MICE, KNOCKOUT; MUTATION; NEURONS; OBESITY; PREOPTIC AREA; PRO-OPIOMELANOCORTIN; REPRODUCTION;

EID: 84879164536     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.5287-12.2013     Document Type: Article

References (38)

1. Abreu AP, Trarbach EB, de Castro M, Frade Costa EM, Versiani B, Matias Baptista MT, Garmes HM, Mendonca BB, Latronico AC (2008) Loss-of-function mutations in the genes encoding prokineticin-2 or prokineticin receptor-2 cause autosomal recessive Kallmann syndrome. J Clin Endocrinol Metab 93:4113-4118. CrossRef Medline
2. Arble DM, Vitaterna MH, Turek FW (2011) Rhythmic leptin is required for weight gain from circadian desynchronized feeding in the mouse. PLoS One 6:e25079. CrossRef Medline
3. Balthasar N, Coppari R, McMinn J, Liu SM, Lee CE, Tang V, Kenny CD, McGovern RA, Chua SC Jr, Elmquist JK, Lowell BB (2004) Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42:983-991. CrossRef Medline
4. Brockschnieder D, Lappe-Siefke C, Goebbels S, Boesl MR, Nave KA, Riethmacher D (2004) Cell depletion due to diphtheria toxin fragment A after Cre-mediated recombination. Mol Cell Biol 24:7636-7642. CrossRef Medline
5. Campbell RE, ffrench-Mullen JM, Cowley MA, Smith MS, Grove KL (2001) Hypothalamic circuitry of neuropeptide Y regulation of neuroendocrine function and food intake via the Y5 receptor subtype. Neuroendocrinology 74:106-119. CrossRef Medline
6. Collin M, Bäckberg M, Ovesjö ML, Fisone G, Edwards RH, Fujiyama F, Meister B (2003) Plasma membrane and vesicular glutamate transporter mRNAs/proteins in hypothalamic neurons that regulate body weight. Eur J Neurosci 18:1265-1278. CrossRef Medline
7. Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL, Cone RD, Low MJ (2001) Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480-484. CrossRef Medline
8. Crown A, Clifton DK, Steiner RA (2007) Neuropeptide signaling in the integration of metabolism and reproduction. Neuroendocrinology 86:175-182. CrossRef Medline
9. Dodé C, Teixeira L, Levilliers J, Fouveaut C, Bouchard P, Kottler ML, Lespinasse J, Lienhardt-Roussie A, Mathieu M, Moerman A, Morgan G, Murat A, Toublanc JE, Wolczynski S, Delpech M, Petit C, Young J, Hardelin JP (2006) Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet 2:e175. CrossRef Medline
10. Elias CF, Lee C, Kelly J, Aschkenasi C, Ahima RS, Couceyro PR, Kuhar MJ, Saper CB, Elmquist JK (1998) Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron 21:1375-1385. CrossRef Medline
11. Elmquist JK (2001) Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin. Int J Obes Relat Metab Disord 25 [Suppl 5]:S78-S82.
12. Fox DL, Good DJ (2008) Nescient helix-loop-helix 2 interacts with signal transducer and activator of transcription 3 to regulate transcription of prohormone convertase 1/3. Mol Endocrinol 22:1438-1448. CrossRef Medline
13. Good DJ, Porter FD, Mahon KA, Parlow AF, Westphal H, Kirsch IR (1997) Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene. Nat Genet 15:397-401. CrossRef Medline
14. Haisenleder DJ, Schoenfelder AH, Marcinko ES, Geddis LM, Marshall JC (2011) Estimation of estradiol in mouse serum samples: evaluation of commercial estradiol immunoassays. Endocrinology 152:4443-4447. CrossRef Medline
15. Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L, Montague CT, Hutton JC, O'Rahilly S (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16:303-306. CrossRef Medline
16. Jing E, Nillni EA, Sanchez VC, Stuart RC, Good DJ (2004) Deletion of the Nhlh2 transcription factor decreases the levels of the anorexigenic pep tides alpha melanocyte-stimulating hormone and thyrotropin-releasing hormone and implicates prohormone convertases I and II in obesity. Endocrinology 145:1503-1513. CrossRef Medline
17. Jordan SD, Kruger M, Willmes DM, Redemann N, Wunderlich FT, Brönneke HS, Merkwirth C, Kashkar H, Olkkonen VM, Böttger T, Braun T, Seibler J, Bruning JC (2011) Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism. Nat Cell Biol 13:434-446. CrossRef Medline
18. Kaelin CB, Xu AW, Lu XY, Barsh GS (2004) Transcriptional regulation of agouti-related protein (Agrp) in transgenic mice. Endocrinology 145: 5798-5806. CrossRef Medline
19. Kruger M, Ruschke K, Braun T (2004) NSCL-1 and NSCL-2 synergistically determine the fate of GnRH-1 neurons and control necdin gene expression. EMBO J 23:4353-4364. CrossRef Medline
20. Lempp R (1957) Adiposogenital dystrophy and puberal obesity (in German). Z Mensch Vererb Konstitutionsl 34:289-302. Medline
21. Ley CJ, Lees B, Stevenson JC (1992) Sex and menopause-associated changes in body-fat distribution. Am J Clin Nutr 55:950-954. Medline
22. Li C, Chen P, Smith MS (1999) Morphological evidence for direct interaction between arcuate nucleus neuropeptide Y (NPY) neurons and gonadotropin-releasing hormone neurons and the possible involvement of NPY Y1 receptors. Endocrinology 140:5382-5390. CrossRef Medline
23. Mattiasson I, Rendell M, Törnquist C, Jeppsson S, Hulthén UL (2002) Effects of estrogen replacement therapy on abdominal fat compartments as related to glucose and lipid metabolism in early postmenopausal women. Horm Metab Res 34:583-588. CrossRef Medline
24. Mayer C, Acosta-Martinez M, Dubois SL, Wolfe A, Radovick S, Boehm U, Levine JE (2010) Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons. Proc Natl Acad Sci U S A 107:22693-22698. CrossRef Medline
25. Ostberg JE, Thomas EL, Hamilton G, Attar MJ, Bell JD, Conway GS (2005) Excess visceral and hepatic adipose tissue in Turner syndrome determined by magnetic resonance imaging: estrogen deficiency associated with hepatic adipose content. J Clin Endocrinol Metab 90:2631-2635. CrossRef Medline
26. Parent AS, Teilmann G, Juul A, Skakkebaek NE, Toppari J, Bourguignon JP (2003) The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr Rev 24:668-693. CrossRef Medline
27. Raposinho PD, Broqua P, Pierroz DD, Hayward A, Dumont Y, Quirion R, Junien JL, Aubert ML (1999) Evidence that the inhibition of luteinizing hormone secretion exerted by central administration of neuropeptide Y (NPY) in the rat is predominantly mediated by the NPY-Y5 receptor subtype. Endocrinology 140:4046-4055. CrossRef Medline
28. Roa J, García-Galiano D, Castellano JM, Gaytan F, Pinilla L, Tena-Sempere M (2010) Metabolic control of puberty onset: new players, new mechanisms. Mol Cell Endocrinol 324:87-94. CrossRef Medline
29. Sarfati J, Guiochon-Mantel A, Rondard P, Arnulf I, Garcia-Piñero A, Wolczynski S, Brailly-Tabard S, Bidet M, Ramos-Arroyo M, Mathieu M, Lienhardt-Roussie A, Morgan G, Turki Z, Bremont C, Lespinasse J, Du Boullay H, Chabbert-Buffet N, Jacquemont S, Reach G, De Talence N, et al. (2010) A comparative phenotypic study of kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes. J Clin Endocrinol Metab 95:659-669. CrossRef Medline
30. Schwenk F, Baron U, Rajewsky K (1995) A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells. Nucleic Acids Res 23:5080-5081. CrossRef Medline
31. Sisk CL, Foster DL (2004) The neural basis of puberty and adolescence. Nat Neurosci 7:1040-1047. CrossRef Medline
32. Sotonyi P, Mezei G, Racz B, Dallman MF, Abizaid A, Horvath TL (2010) Gonadotropin-releasing hormone fibers contact POMC neurons in the hypothalamic arcuate nucleus. Reprod Sci 17:1024-1028. CrossRef Medline
33. van den Top M, Lee K, Whyment AD, Blanks AM, Spanswick D (2004) Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus. Nat Neurosci 7:493-494. CrossRef Medline
34. Vella KR, Burnside AS, Brennan KM, Good DJ (2007) Expression of the hypothalamic transcription factor Nhlh2 is dependent on energy availability. J Neuroendocrinol 19:499-510. CrossRef Medline
35. Wankhade UD, Good DJ (2011) Melanocortin 4 receptor is a transcriptional target of nescient helix-loop-helix-2. Mol Cell Endocrinol 341:39-47. CrossRef Medline
36. Yaswen L, Diehl N, Brennan MB, Hochgeschwender U (1999) Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 5:1066-1070. CrossRef Medline
37. Yepuru M, Eswaraka J, Kearbey JD, Barrett CM, Raghow S, Veverka KA, Miller DD, Dalton JT, Narayanan R (2010) Estrogen receptor--selective ligands alleviate high-fat diet-and ovariectomy-induced obesity in mice. J Biol Chem 285:31292-31303. CrossRef Medline
38. Yoon H, Enquist LW, Dulac C (2005) Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Cell 123:669-682. CrossRef Medline