Leptin activates hypothalamic CART neurons projecting to the spinal cord

Neuron

Volumn 21, Issue 6, 1998, Pages 1375-1385

  Elias, Carol F ^a,b   Lee, Charlotte ^b   Kelly, Joseph ^b   Aschkenasi, Carl ^b   Ahima, Rexford S ^b   Couceyro, Pastor R ^c   Kuhar, Michael J ^c   Saper, Clifford B ^a   Elmquist, Joel K ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^c EMORY UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMPHETAMINE; COCAINE; LEPTIN; MESSENGER RNA; PROOPIOMELANOCORTIN; RECOMBINANT LEPTIN;

ADIPOCYTE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; ENERGY EXPENDITURE; HISTOPATHOLOGY; HYPOTHALAMUS; INTRAVENOUS DRUG ADMINISTRATION; MALE; NERVE CELL; NEUROMODULATION; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; RAT; THERMOGENESIS; TRANSCRIPTION REGULATION;

EID: 0032436307     PISSN: 08966273     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0896-6273(00)80656-X     Document Type: Article

References (76)

1. Ahima, R.S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., and Flier, J.S. (1996). Role of leptin in the neuroendocrine response to fasting. Nature 382, 250-252.
2. Breder, C D., Smith, W.L., Raz, A., Masferrer, J., Seibert, K., Needleman, P., and Saper, C.B. (1992). Distribution and characterization of cyclooxygenase immunoreactivity in the ovine brain. J. Comp. Neurol. 322, 409-438.
3. Campfield, L.A., Smith, F.J., Guisez, Y., Devos, R., and Burn, P. (1995). Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269, 546-549.
4. Campfield, L.A., Smith, F.J., and Burn, P. (1998). Strategies and potential molecular targets for obesity treatment. Science 280, 1383-1387.
5. Caro, J.F., Sinha, M.K., Kolaczynski, J.W., Zhang, P.L., and Considine, R.V. (1996). Leptin: the tale of an obesity gene. Diabetes 45, 1455-1462.
6. Casto, R.M., VanNess, J.M., and Overton, J.M. (1998). Effects of central leptin administration on blood pressure in normotensive rats. Neurosci. Lett. 246, 29-32.
7. Cechetto, D.F., and Saper, C.B. (1988). Neurochemical organization of the hypothalamic projection to the spinal cord in the rat. J. Comp. Neurol. 272, 579-604.
8. Chan, R.K., and Sawchenko, P.E. (1995). Hemodynamic regulation of tyrosine hydroxylase messenger RNA in medullary catecholamine neurons: a c-fos-guided hybridization histochemical study. Neuroscience 66, 377-390.
9. Chan, R.K., Brown, E.R., Ericsson, A., Kovacs, K.J., and Sawchenko, P.E. (1993). A comparison of two immediate-early genes, c-fos and NGFI-B, as markers for functional activation in stress-related neuroendocrine circuitry. J. Neurosci. 13, 5126-5138.
10. Cheung, C.C., Clifton, D.K., and Steiner, R.A. (1997). Prooplomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138, 4489-4492.
11. Collins, S., Kuhn, C.M., Petro, A.E., Swick, A.G., Chrunyk, B.A., and Surwit, R.S. (1996). Role of leptin in fat regulation. Nature 380, 677.
12. Couceyro, P.R., Koylu, E.O., and Kuhar, M.J. (1997). Further studies on the anatomical distribution of CART by in situ hybridization. J. Chem. Neuroanat. 12, 229-241.
13. Dawson, R., Pelleymounter, M.A,, Millard, W.J., Liu, S., and Eppler, B. (1997). Attenuation of leptin-mediated effects by monosodium glutamate-induced arcuate nucleus damage. Am. J. Physiol. 273, E202-E206.
14. De Lacalle, S., Hersh, L.B., and Saper, C.B. (1993). Cholinergic innervation of the human cerebellum. J. Comp. Neurol. 328, 364-376.
15. Douglass, J., McKinzie, A.A., and Couceyro, P. (1995). PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine. J. Neurosci. 15, 2471-2481.
16. Elias, C.F., Saper, C.B., Maratos-Flier, E., Tritos, N.A., Lee, C., Kelly, J., Tatro, J.B., Huffman, G.E., Ollmann, M.M., Barsh, G.S., et al. (1998). Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J. Comp. Neurol., in press.
17. Elmquist, J.K., and Saper, C.B. (1996). Activation of neurons projecting to the para ventricular hypothalamic nucleus by intravenous lipopolysaccharide. J. Comp. Neurol. 374, 315-331.
18. Elmquist, J.K., Scammell, T.E., Jacobson, C.D., and Saper, C.B. (1996). Distribution of Fos-like immune-reactivity in the rat brain following intravenous lipopolysaccharide administration. J. Comp. Neurol. 371, 85-103.
19. Elmquist, J.K., Ahima, R.S., Maratos-Flier, E., Flier, J.S., and Saper, C.B. (1997). Leptin activates neurons in ventrobasal hypothalamus and brainstem. Endocrinology 138, 839-842.
20. Elmquist, J.K., Bjorbaek, C., Ahima, R.S., Flier, J.S., and Saper, C.B. (1998a). Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol. 395, 535-547.
21. Elmquist, J.K., Ahima, R.S., Elias, C.F., Flier, J.S., and Saper, C.B. (1998b). Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei. Proc. Natl. Acad. Sci. USA 95, 741-746.
22. Fan, W., Boston, B.A., Kesterson, R.A., Hruby, V.J., and Cone, R.D. (1997). Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385, 165-168.
23. Fei, H., Okano, H.J., Li, C., Lee, G.H., Zhao, C., Darnell, R., and Friedman, J.M. (1997). Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues. Proc. Natl. Acad. Sci. USA 94, 7001-7005.
24. Foster, D.O., Depocas, F., and Zuker, M. (1982). Heterogeneity of the sympathetic innervation of rat interscapular brown adipose tissue via intercostal nerves. Can. J. Physiol. Pharmacol. 60, 747-754.
25. Gold, R.M. (1973). Hypothalamic obesity: the myth of the ventromedial nucleus. Science 182, 488-490.
26. Hahn, T., Breininger, J., Baskin, D., and Schwartz, M. (1998). Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat. Neurosci. 1, 271-272.
27. Hakansson, M.L., Brown, H., Ghilardi, N., Skoda, R.C., and Meister, B. (1998). Leptin receptor immune-reactivity in chemically defined target neurons of the hypothalamus. J. Neurosci. 18, 559-572.
28. Halaas, J.L., Gajiwala, K.S., Maffei, M., Cohen, S.L., Chait, B.T., Rabinowitz, D., Lallone, R.L., Burley, S.K., and Friedman, J.M. (1995). Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269, 543-546.
29. Haynes, W.G., Morgan, D.A., Walsh, S.A., Mark, A.L., and Sivitz, W.I. (1997). Receptor-mediated regional sympathetic nerve activation by leptin. J. Clin. Invest. 100, 270-278.
30. Huszar, D., Lynch, C.A., Fairchild-Huntress, V., Dunmore, J.H., Fang, Q., Berkemeier, L.R., Gu, W., Kesterson, R.A., Boston, B.A., Cone, R.D., et al. (1997). Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131-141.
31. Jacobowitz, D.M., and O'Donohue, T.L. (1978). α-Melanocyte stimulating hormone: immunohistochemical identification and mapping in neurons of rat brain. Proc. Natl. Acad. Sci. USA 75, 6300-6304.
32. Joseph, S.A., Pilcher, W.H., and Bennett-Clarke, C. (1983). Immunocytochemical localization of ACTH perikarya in nucleus tractus solitarius: evidence for a second opiocortin neuronal system. Neurosci. Lett. 38, 221-225.
33. Kelly, A.B., and Watts, A.G. (1996). Mediation of dehydration-induced peptidergic gene expression in the rat lateral hypothalamic area by forebrain afferent projections. J. Comp. Neurol. 370, 231-246.
34. Koylu, E.O., Couceyro, P.R., Lambert, P.D., Ling, N.C., DeSouza, E.B., and Kuhar, M.J. (1997). Immunohistochemical localization of novel CART peptides in rat hypothalamus, pituitary and adrenal gland. J. Neuroendocrinol. 9, 823-833.
35. Koylu, E.O., Couceyro, P.R., Lambert, P.D., and Kuhar, M.J. (1998). Cocaine- and amphetamine-regulated transcript peptide immunohistochemical localization in the rat brain. J. Comp. Neurol. 391, 115-132.
36. Kristensen, P., Judge, M.E., Thim, L., Ribel, U., Christjansen, K.N., Wulff, B.S., Clausen, J.T., Jensen, P.B., Madsen, O.D., Vrang, N., et al. (1998). Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 393, 72-76.
37. Lambert, P.D., Couceyro, P.R., Koylu, E.O., Ling, N.C., DeSouza, E.B., and Kuhar, M.J. (1997). A role for novel CART peptide fragments in the central control of food intake. Neuropeptides 31, 620-621.
38. Lambert, P.D., Couceyro, P.R., McGirr, K.M., Vechia, S.E., Smith, Y., and Kuhar, M.J. (1998). CART peptides in the central control of feeding and interactions with neuropeptide Y. Synapse 29, 293-298.
39. Leibowitz, S.F. (1991). Brain neuropeptide Y: an integrator of endocrine, metabolic and behavioral processes. Brain Res. Bull. 27, 333-337.
40. Levin, N., Nelson, C., Gurney, A., Vandlen, R., and de Sauvage, F. (1996). Decreased food intake does not completely account for adiposity reduction after ob protein infusion. Proc. Natl. Acad. Sci. USA 93, 1726-1730.
41. Loewy, A.D. (1991). Forebrain nuclei involved in autonomic control. Prog. Brain Res. 87, 253-268.
42. Lowell, B.B., and Flier, J.S. (1997). Brown adipose tissue, beta 3-adrenergic receptors, and obesity. Annu. Rev. Med. 48, 307-316.
43. Lowell, B.B., S.-Susulic, V., Hamann, A., Lawitts, J.A., Himms-Hagen, J., Boyer, B.B., Kozak, L.P., and Flier, J.S. (1993). Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366, 740-742.
44. Luiten, P.G., ter Horst, G.J., Karst, H., and Steffens, A.B. (1985). The course of paraventricular hypothalamic efferents to autonomic structures in medulla and spinal cord. Brain Res. 329, 374-378.
45. Marks, D.L., Wiemann, J.N., Burton, K.A., Lent, K.L., Clifton, D.K., and Steiner, R.A. (1992). Simultaneous visualization of two cellular mRNA species in individual neurons by use of a new double in situ hybridization method. Mol. Cell. Neurosci. 3, 395-405.
46. Mercer, J.G., Hoggard, N., Williams, L.M., Lawrence, C.B., Hannah, L.T., and Trayhurn, P. (1996). Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization. FEBS Lett. 387, 113-116.
47. Mizuno, T.M., Kleopoulos, S.P., Bergen, H.T., Roberts, J.L., Priest, C.A., and Mobbs, C.V. (1998). Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting in ob/ob and db/db mice, but is stimulated by leptin. Diabetes 47, 294-297.
48. Ollmann, M.M., Wilson, B.D., Yang, Y.K., Kerns, J.A., Chen, Y., Gantz, I., and Barsh, G.S. (1997). Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278, 135-138.
49. Paxinos, G., and Watson, C. (1997). The rat brain, in stereotaxic coordinates. Compact, Third Edition (San Diego: Academic Press).
50. Pelleymounter, M.A., Cullen, M.J., Baker, M.B., Hecht, R., Winters, D., Boone, T., and Collins, F. (1995). Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540-543.
51. Rothwell, N.J., and Stock, M.J. (1984). Effects of denervating brown adipose tissue on the responses to cold, hyperphagia and noradrenaline treatment in the rat. J. Physiol. (Lond) 355, 457-463.
52. Saito, M., Minokoshi, Y., and Shimazu, T. (1989). Accelerated norepinephrine turnover in peripheral tissues after ventromedial hypothalamic stimulation in rats. Brain Res. 481, 298-303.
53. Sakaguchi, T., Bray, G.A., and Eddlestone, G. (1988). Sympathetic activity following paraventricular or ventromedial hypothalamic lesions in rats. Brain Res. Bull. 20, 461-465.
54. Saper, C.B. (1995). Central autonomic system. In The Rat Nervous System, G. Paxinos, ed. (San Diego: Academic Press), pp. 107-135.
55. Saper, C.B., Loewy, A.D., Swanson, L.W., and Cowan, W.M. (1976). Direct hypothalamo-autonomic connections. Brain Res. 117, 305-312.
56. Satoh, N., Ogawa, Y., Katsuura, G., Numata, Y., Masuzaki, H., Yoshimasa, Y., and Nakao, K. (1998). Satiety effect and sympathetic activation of leptin are mediated by hypothalamic melanocortin system. Neurosci. Lett. 249, 107-110.
57. Sawchenko, P.E., and Swanson, L.W. (1982). Immunohistochemical identification of neurons in the paraventricular nucleus of the hypothalamus that project to the medulla or to the spinal cord in the rat. J Comp. Neurol. 205, 260-272.
58. Scarpace, P.J., Matheny, M., Pollock, B.H., and Tumer, N. (1997). Leptin increases uncoupling protein expression and energy expenditure. Am. J. Physiol. 273, E226-E230.
59. Schwarte, M.W., Seeley, R.J., Campfield, L.A., Burn, P., and Baskin, D.G. (1996). Identification of targets of leptin action in rat hypothalamus. J. Clin. Invest. 98, 1101-1106.
60. Schwartz, M.W., Seeley, R.J., Woods, S.C., Weigle, D.S., Campfield, L.A., Burn, P., and Baskin, D.G. (1997). Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 46, 2119-2123.
61. Seeley, R.J., Yagaloff, K.A., Fisher, S.L., Burn, P., Thiele, T.E., van Dijk, G., Baskin, D.G., and Schwartz, M.W. (1997). Melanocortin receptors in leptin effects. Nature 390, 349.
62. Simmons, D.M., Arriza, J.L., and Swanson, L.W. (1989). A complete protocol for in situ hybridization of messenger RNAs in brain and other tissues with radiolabelled single stranded RNA probes. J. Histotech. 12, 169-181.
63. Spiegelman, B.M., and Flier, J.S. (1996). Adipogenesis and obesity: rounding out the big picture. Cell 87, 377-389.
64. Strack, A.M., Sawyer, W.B., Hughes, J.H., Platt, K.B., and Loewy, A.D. (1989). A general pattern of CNS innervation of the sympathetic outflow demonstrated by transneuronal pseudorabies viral infections. Brain Res. 491, 156-162.
65. Swanson, L.W. (1992). Brain Maps: Structure of the Rat Brain, Volume 1 (Amsterdam: Elsevier).
66. Swanson, L.W., and Kuypers, H.G. (1980). A direct projection from the ventromedial nucleus and retrochiasmatic area of the hypothalamus to the medulla and spinal cord of the rat. Neurosci. Lett. 17, 307-312.
67. Swanson, L.W., and Sawchenko, P.E. (1983). Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. Annu. Rev. Neurosci. 6, 269-324.
68. Swanson, L.W., Sawchenko, P.E., Wiegand, S.J., and Price, J.L. (1980). Separate neurons in the paraventricular nucleus project to the median eminence and to the medulla or spinal cord. Brain Res. 198, 190-195.
69. Tatro, J.B., and Reichlin, S. (1987). Specific receptors for α-melanocyte-stimulating hormone are widely distributed in tissues of rodents. Endocrinology 121, 1900-1907.
70. Thornton, J.E., Cheung, C.C., Clifton, D.K., and Steiner, R.A. (1997). Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology 138, 5063-5066.
71. Van Dijk, G., Thiele, T.E., Donahey, J.C., Campfield, L.A., Smith, F.J. Burn, P., Bernstein, I.L., Woods, S.C., and Seeley, R.J. (1996). Central infusions of leptin and GLP-1-(7-36) amide differentially stimulate c-FLI in the rat brain. Am. J. Physiol. 271, R1096-R1100.
72. Wang, L., Martinez, V., Barrachina, M.D., and Tache, Y. (1998). Fos expression in the brain induced by peripheral injection of CCK or leptin plus CCK in fasted lean mice. Brain Res. 791, 157-166.
73. Watson, S.J., Akil, H., Richard, C W.D., and Barchas, J.D. (1978). Evidence for two separate opiate peptide neuronal systems. Nature 275, 226-228.
74. Woods, S.C., Seeley, R.J., Porte, D., Jr., and Schwartz, M.W. (1998). Signals that regulate food intake and energy homeostasis. Science 280, 1378-1383.
75. Yoshimatsu, H., Egawa, M., and Bray, G.A. (1993). Sympathetic nerve activity after discrete hypothalamic injections of L-glutamate. Brain Res. 601, 121-128.
76. Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., and Friedman, J.M. (1994). Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425-432.