Defining a novel leptin–melanocortin–kisspeptin pathway involved in the metabolic control of puberty

Molecular Metabolism

Volumn 5, Issue 10, 2016, Pages 844-857

  Manfredi Lozano, Maria ^a,b,c   Roa, Juan ^a,b,c,d   Ruiz Pino, Francisco ^a,b,c,d   Piet, Richard ^f   Garcia Galiano, David ^a,b   Pineda, Rafael ^a   Zamora, Aurora ^a,b   Leon, Silvia ^a,b   Sanchez Garrido, Miguel A ^a,b,d   Romero Ruiz, Antonio ^a,b   Dieguez, Carlos ^e   Vazquez, Maria Jesus ^a,b,c,d   Herbison, Allan E ^f   Pinilla, Leonor ^a,b,c,d   Tena Sempere, Manuel ^a,b,c,d  

^a Maimonides Institute for Research in Biomedicine of Cordoba   (Spain)

^b UNIVERSITY OF CÓRDOBA   (Spain)

^c HOSPITAL UNIVERSITARIO REINA SOFÍA   (Spain)

^d INSTITUTO DE SALUD CARLOS III   (Spain)

^e Universidade de Santiago de Compostela and Instituto de Investigación Sanitaria de Santiago de Compostela   (Spain)

^f UNIVERSITY OF OTAGO   (New Zealand)

Author keywords

DREADDs; Kisspeptin; Leptin; Metabolism; Puberty; MSH

Indexed keywords

ALPHA INTERMEDIN; G PROTEIN COUPLED RECEPTOR 54; KISSPEPTIN; KISSPEPTIN 1; LEPTIN; MELANOCORTIN; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DELAYED PUBERTY; DNA MODIFICATION; ELECTROPHYSIOLOGY; FEMALE; FUNCTIONAL GENOMICS; MALE; METABOLIC REGULATION; MOUSE; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PUBERTY; RAT; RECEPTOR UPREGULATION; REPRODUCTION; SIGNAL TRANSDUCTION; WILD TYPE MOUSE; WILD TYPE RAT;

EID: 84992193593     PISSN: None     EISSN: 22128778     Source Type: Journal    
DOI: 10.1016/j.molmet.2016.08.003     Document Type: Article

References (60)

1. [1] Parent, A.S., Teilmann, G., Juul, A., Skakkebaek, N.E., Toppari, J., Bourguignon, J.P., The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocrine Reviews 24 (2003), 668–693.
2. [2] Aksglaede, L., Juul, A., Olsen, L.W., Sorensen, T.I., Age at puberty and the emerging obesity epidemic. PLoS One, 4, 2009, e8450.
3. [3] De Leonibus, C., Marcovecchio, M.L., Chiavaroli, V., de Giorgis, T., Chiarelli, F., Mohn, A., Timing of puberty and physical growth in obese children: a longitudinal study in boys and girls. Pediatric Obesity 9 (2013), 292–299.
4. [4] Day, F.R., Elks, C.E., Murray, A., Ong, K.K., Perry, J.R., Puberty timing associated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study. Scientific Reports, 5, 2015, 11208.
5. [5] Lakshman, R., Forouhi, N.G., Sharp, S.J., Luben, R., Bingham, S.A., Khaw, K.T., et al. Early age at menarche associated with cardiovascular disease and mortality. The Journal of Clinical Endocrinology and Metabolism 94 (2009), 4953–4960.
6. [6] Pinilla, L., Aguilar, E., Dieguez, C., Millar, R.P., Tena-Sempere, M., Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiological Reviews 92 (2012), 1235–1316.
7. [7] Roa, J., Role of GnRH neurons and their neuronal afferents as key integrators between food intake regulatory signals and the control of reproduction. International Journal of Endocrinology, 2013, 2013, 518046.
8. [8] Elias, C.F., Leptin action in pubertal development: recent advances and unanswered questions. Trends in Endocrinology and Metabolism 23 (2012), 9–15.
9. [9] Quennell, J.H., Mulligan, A.C., Tups, A., Liu, X., Phipps, S.J., Kemp, C.J., et al. Leptin indirectly regulates gonadotropin-releasing hormone neuronal function. Endocrinology 150 (2009), 2805–2812.
10. [10] Seminara, S.B., Messager, S., Chatzidaki, E.E., Thresher, R.R., Acierno, J.S. Jr., Shagoury, et al. The GPR54 gene as a regulator of puberty. New England Journal of Medicine 349 (2003), 1614–1627.
11. [11] de Roux, N., Genin, E., Carel, J.C., Matsuda, F., Chaussain, J.L., Milgrom, E., Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proceedings of the National Academy of Sciences of the United States of America 100 (2003), 10972–10976.
12. [12] Clarkson, J., Han, S.K., Liu, X., Lee, K., Herbison, A.E., Neurobiological mechanisms underlying kisspeptin activation of gonadotropin-releasing hormone (GnRH) neurons at puberty. Molecular and Cellular Endocrinology 324 (2010), 45–50.
13. [13] Navarro, V.M., Tena-Sempere, M., Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility. Nature Reviews Endocrinology 8 (2012), 40–53.
14. [14] Sanchez-Garrido, M.A., Ruiz-Pino, F., Manfredi-Lozano, M., Leon, S., Garcia-Galiano, D., Castano, J.P., et al. Obesity-induced hypogonadism in the male: premature reproductive neuroendocrine senescence and contribution of Kiss1-mediated mechanisms. Endocrinology 155 (2014), 1067–1079.
15. [15] Donato, J. Jr., Cravo, R.M., Frazao, R., Gautron, L., Scott, M.M., Lachey, J., et al. Leptin's effect on puberty in mice is relayed by the ventral premammillary nucleus and does not require signaling in Kiss1 neurons. Journal of Clinical Investigation 121 (2011), 355–368.
16. [16] Xu, Y., Faulkner, L.D., Hill, J.W., Cross-talk between metabolism and reproduction: the role of POMC and SF1 neurons. Frontiers in Endocrinology, 2, 2012, 98.
17. [17] Dores, R.M., Londraville, R.L., Prokop, J., Davis, P., Dewey, N., Lesinski, N., Molecular evolution of GPCRs: melanocortin/melanocortin receptors. Journal of Molecular Endocrinology 52 (2014), T29–T42.
18. [18] Wilson, J.L., Enriori, P.J., A talk between fat tissue, gut, pancreas and brain to control body weight. Molecular and Cellular Endocrinology 418 (2015), 108–119.
19. [19] Elias, C.F., Purohit, D., Leptin signaling and circuits in puberty and fertility. Cellular and Molecular Life Sciences 70 (2012), 841–862.
20. [20] Huszar, D., Lynch, C.A., Fairchild-Huntress, V., Dunmore, J.H., Fang, Q., Berkemeier, L.R., et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88 (1997), 131–141.
21. [21] Butler, A.A., Cone, R.D., The melanocortin receptors: lessons from knockout models. Neuropeptides 36 (2002), 77–84.
22. [22] Granholm, N.H., Jeppesen, K.W., Japs, R.A., Progressive infertility in female lethal yellow mice (Ay/a; strain C57BL/6J). Journal of Reproduction and Fertility 76 (1986), 279–287.
23. [23] Israel, D.D., Sheffer-Babila, S., de Luca, C., Jo, Y.H., Liu, S.M., Xia, Q., et al. Effects of leptin and melanocortin signaling interactions on pubertal development and reproduction. Endocrinology 153 (2012), 2408–2419.
24. [24] Sheffer-Babila, S., Sun, Y., Israel, D.D., Liu, S.M., Neal-Perry, G., Chua, S.C. Jr., Agouti-related peptide plays a critical role in leptin's effects on female puberty and reproduction. American Journal of Physiology. Endocrinology and Metabolism 305 (2013), E1512–E1520.
25. [25] Backholer, K., Smith, J., Clarke, I.J., Melanocortins may stimulate reproduction by activating orexin neurons in the dorsomedial hypothalamus and kisspeptin neurons in the preoptic area of the ewe. Endocrinology 150 (2009), 5488–5497.
26. [26] Cravo, R.M., Margatho, L.O., Osborne-Lawrence, S., Donato, J. Jr., Atkin, S., Bookout, A.L., et al. Characterization of Kiss1 neurons using transgenic mouse models. Neuroscience 173 (2011), 37–56.
27. [27] Backholer, K., Smith, J.T., Rao, A., Pereira, A., Iqbal, J., Ogawa, S., et al. Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells. Endocrinology 151 (2010), 2233–2243.
28. [28] Fu, L.Y., van den Pol, A.N., Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism. The Journal of Neuroscience 30 (2010), 10205–10219.
29. [29] Garcia-Galiano, D., van Ingen Schenau, D., Leon, S., Krajnc-Franken, M.A., Manfredi-Lozano, M., Romero-Ruiz, A., et al. Kisspeptin signaling is indispensable for neurokinin B, but not glutamate, stimulation of gonadotropin secretion in mice. Endocrinology 153 (2012), 316–328.
30. [30] Gottsch, M.L., Popa, S.M., Lawhorn, J.K., Qiu, J., Tonsfeldt, K.J., Bosch, M.A., et al. Molecular properties of Kiss1 neurons in the arcuate nucleus of the mouse. Endocrinology 152 (2011), 4298–4309.
31. [31] Mayer, C., Acosta-Martinez, M., Dubois, S.L., Wolfe, A., Radovick, S., Boehm, U., et al. Timing and completion of puberty in female mice depend on estrogen receptor alpha-signaling in kisspeptin neurons. Proceedings of the National Academy of Sciences of the United States of America 107 (2010), 22693–22698.
32. [32] Roa, J., Garcia-Galiano, D., Varela, L., Sanchez-Garrido, M.A., Pineda, R., Castellano, J.M., et al. The mammalian target of rapamycin as novel central regulator of puberty onset via modulation of hypothalamic Kiss1 system. Endocrinology 150 (2009), 5016–5026.
33. [33] Navarro, V.M., Ruiz-Pino, F., Sanchez-Garrido, M.A., Garcia-Galiano, D., Hobbs, S.J., Manfredi-Lozano, M., et al. Role of neurokinin B in the control of female puberty and its modulation by metabolic status. The Journal of Neuroscience 32 (2012), 2388–2397.
34. [34] Paxinos, G., Franklin, K.B.J., The mouse brain in stereotaxic coordinates. Vol. 2, 2001, Academic Press, San Diego.
35. [35] Watanobe, H., Yoneda, M., Kakizaki, Y., Kohsaka, A., Suda, T., Schioth, H.B., Further evidence for a significant participation of the melanocortin 4 receptor in the preovulatory prolactin surge in the rat. Brain Research Bulletin 54 (2001), 521–525.
36. [36] Watanobe, H., Schioth, H.B., Wikberg, J.E., Suda, T., The melanocortin 4 receptor mediates leptin stimulation of luteinizing hormone and prolactin surges in steroid-primed ovariectomized rats. Biochemical and Biophysical Research 257 (1999), 860–864.
37. [37] Garcia-Galiano, D., Pinilla, L., Tena-Sempere, M., Sex steroids and the control of the Kiss1 system: developmental roles and major regulatory actions. Journal of Neuroendocrinology 24 (2012), 22–33.
38. [38] Armbruster, B.N., Li, X., Pausch, M.H., Herlitze, S., Roth, B.L., Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proceedings of the National Academy of Sciences of the United States of America 104 (2007), 5163–5168.
39. [39] Balthasar, N., Coppari, R., McMinn, J., Liu, S.M., Lee, C.E., Tang, V., et al. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 42 (2004), 983–991.
40. [40] Kirilov, M., Clarkson, J., Liu, X., Roa, J., Campos, P., Porteous, R., et al. Dependence of fertility on kisspeptin-Gpr54 signaling at the GnRH neuron. Nature Communications, 4, 2013, 2492.
41. [41] de Croft, S., Piet, R., Mayer, C., Mai, O., Boehm, U., Herbison, A.E., Spontaneous kisspeptin neuron firing in the adult mouse reveals marked sex and brain region differences but no support for a direct role in negative feedback. Endocrinology 153 (2012), 5384–5393.
42. [42] Garfield, A.S., Lam, D.D., Marston, O.J., Przydzial, M.J., Heisler, L.K., Role of central melanocortin pathways in energy homeostasis. Trends in Endocrinology and Metabolism 20 (2009), 203–215.
43. [43] Corander, M.P., Coll, A.P., Melanocortins and body weight regulation: glucocorticoids, Agouti-related protein and beyond. European Journal of Pharmacology 660 (2011), 111–118.
44. [44] Reid, R.L., Ling, N., Yen, S.S., Gonadotropin-releasing activity of alpha-melanocyte-stimulating hormone in normal subjects and in subjects with hypothalamic-pituitary dysfunction. The Journal of Clinical Endocrinology and Metabolism 58 (1984), 773–777.
45. [45] Roa, J., Herbison, A.E., Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY neuron neuropeptides in female mice. Endocrinology 153 (2012), 5587–5599.
46. [46] Raposinho, P.D., Castillo, E., d'Alleves, V., Broqua, P., Pralong, F.P., Aubert, M.L., Chronic blockade of the melanocortin 4 receptor subtype leads to obesity independently of neuropeptide Y action, with no adverse effects on the gonadotropic and somatotropic axes. Endocrinology 141 (2000), 4419–4427.
47. [47] Roa, J., Tena-Sempere, M., Connecting metabolism and reproduction: roles of central energy sensors and key molecular mediators. Molecular and Cellular Endocrinology 397 (2014), 4–14.
48. [48] Hohmann, J.G., Teal, T.H., Clifton, D.K., Davis, J., Hruby, V.J., Han, G., et al. Differential role of melanocortins in mediating leptin's central effects on feeding and reproduction. The American Journal of Physiology Regulatory Integrative Comparative Physiology 278 (2000), R50–R59.
49. [49] Leon, S., Barroso, A., Vazquez, M.J., Garcia-Galiano, D., Manfredi-Lozano, M., Ruiz-Pino, F., et al. Direct actions of kisspeptins on GnRH neurons permit attainment of fertility but are insufficient to fully preserve gonadotropic axis activity. Scientific Reports, 6, 2016, 19206.
50. [50] Stengel, A., Wang, L., Goebel-Stengel, M., Tache, Y., Centrally injected kisspeptin reduces food intake by increasing meal intervals in mice. Neuroreport 22 (2011), 253–257.
51. [51] Martin, C., Navarro, V.M., Simavli, S., Vong, L., Carroll, R.S., Lowell, B.B., et al. Leptin-responsive GABAergic neurons regulate fertility through pathways that result in reduced kisspeptinergic tone. The Journal of Neuroscience 34 (2014), 6047–6056.
52. [52] Zuure, W.A., Roberts, A.L., Quennell, J.H., Anderson, G.M., Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function. The Journal of Neuroscience 33 (2013), 17874–17883.
53. [53] Piet, R., de Croft, S., Liu, X., Herbison, A.E., Electrical properties of kisspeptin neurons and their regulation of GnRH neurons. Frontiers in Neuroendocrinology 36 (2015), 15–27.
54. [54] Bellefontaine, N., Chachlaki, K., Parkash, J., Vanacker, C., Colledge, W., d'Anglemont de Tassigny, X., et al. Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction. Journal of Clinical Investigation 124 (2014), 2550–2559.
55. [55] Pu, S., Horvath, T.L., Diano, S., Naftolin, F., Kalra, P.S., Kalra, S.P., Evidence showing that beta-endorphin regulates cyclic guanosine 3′,5′-monophosphate (cGMP) efflux: anatomical and functional support for an interaction between opiates and nitric oxide. Endocrinology 138 (1997), 1537–1543.
56. [56] Castellano, J.M., Navarro, V.M., Fernandez-Fernandez, R., Castano, J.P., Malagon, M.M., Aguilar, E., et al. Ontogeny and mechanisms of action for the stimulatory effect of kisspeptin on gonadotropin-releasing hormone system of the rat. Molecular and Cellular Endocrinology 257–258 (2006), 75–83.
57. [57] Overgaard, A., Tena-Sempere, M., Franceschini, I., Desroziers, E., Simonneaux, V., Mikkelsen, J.D., Comparative analysis of kisspeptin-immunoreactivity reveals genuine differences in the hypothalamic Kiss1 systems between rats and mice. Peptides 45 (2013), 85–90.
58. [58] Clarkson, J., Herbison, A.E., Postnatal development of kisspeptin neurons in mouse hypothalamus; sexual dimorphism and projections to gonadotropin-releasing hormone neurons. Endocrinology 147 (2006), 5817–5825.
59. [59] Clarkson, J., Boon, W.C., Simpson, E.R., Herbison, A.E., Postnatal development of an estradiol-kisspeptin positive feedback mechanism implicated in puberty onset. Endocrinology 150 (2009), 3214–3220.
60. [60] Sandrock, M., Schulz, A., Merkwitz, C., Schoneberg, T., Spanel-Borowski, K., Ricken, A., Reduction in corpora lutea number in obese melanocortin-4-receptor-deficient mice. Reproductive Biology and Endocrinology, 7, 2009, 24.