¿Cómo participa el cerebro en la obesidad? | 21 ENE 19

Determinantes fisiológicos y culturales de la conducta alimentaria

Determinantes cognitivos y autonómicos en la obesidad. Esta revisión se centra sobre los determinantes de la homeostasis de la energía, como factores importantes para la obesidad, se basa sobre el control del consumo y del gasto de energía
INDICE:  1.  | 2. 

1. Tchernof, A. & Despres, J. P. Pathophysiology of human visceral obesity: an update. Physiol. Rev. 93, 359–404 (2013).
2. Finkelstein, E. A., Trogdon, J. G., Cohen, J. W. & Dietz, W. Annual medical spending attributable to obesity: payer- and service-specific estimates. Health Aff. (Millwood) 28, w822–w831 (2009).
3. Hall, K. D. et al. Energy balance and its components: implications for body weight regulation. Am. J. Clin. Nutr. 95, 989–994 (2012).
4. Foster, D. O. Quantitative contribution of brown adipose tissue thermogenesis to overall metabolism. Can. J. Biochem. Cell. Biol. 62, 618–622 (1984).
5. Chechi, K., Carpentier, A. C. & Richard, D. Understanding the brown adipocyte as a contributor to energy homeostasis. Trends Endocrinol. Metab. 24, 408–420 (2013).
6. Contreras, C. et al. The brain and brown fat. Ann. Med. 47, 1–19 (2015).
7. El-Sayed Moustafa, J. S. & Froguel, P. From obesity genetics to the future of personalized obesity therapy. Nat. Rev. Endocrinol. 9, 402–413 (2013).
8. Lukaszewski, M. A., Eberle, D., Vieau, D. & Breton, C. Nutritional manipulations in the perinatal period program adipose tissue in offspring. Am. J. Physiol. Endocrinol. Metab. 305, E1195–E1207 (2013).
9. Martin-Gronert, M. S. & Ozanne, S. E. Early life programming of obesity. Med. Wieku Rozwoj 17, 7–12 (2013).
10. Williams, L. M. Hypothalamic dysfunction in obesity. Proc. Nutr. Soc. 71, 521–533 (2012).
11. Yon, M. A., Mauger, S. L. & Pickavance, L. C. Relationships between dietary macronutrients and adult neurogenesis in the regulation of energy metabolism. Br. J. Nutr. 109, 1573–1589 (2013).
12. Bouret, S. G. Role of early hormonal and nutritional experiences in shaping feeding behavior and hypothalamic development. J. Nutr. 140, 653–657 (2010).
13. Horvath, T. L. et al. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc. Natl Acad. Sci. USA 107, 14875–14880 (2010).
14. Irani, B. G., Dunn-Meynell, A. A. & Levin, B. E. Altered hypothalamic leptin, insulin, and melanocortin binding associated with moderate-fat diet and predisposition to obesity. Endocrinology 148, 310–316 (2007).
15. Bouret, S. G. et al. Hypothalamic neural projections are permanently disrupted in diet-induced obese rats. Cell Metab. 7, 179–185 (2008).
16. Nieuwdorp, M., Gilijamse, P. W., Pai, N. & Kaplan, L. M. Role of the microbiome in energy regulation and metabolism. Gastroenterology 146, 1525–1533 (2014).
17. Blaut, M. Gut microbiota and energy balance: role in obesity. Proc. Nutr. Soc. http://dx.doi.org/10.1017/S0029665114001700.
18. Cani, P. D. Metabolism in 2013: The gut microbiota manages host metabolism. Nat. Rev. Endocrinol. 10, 74–76 (2014).
19. Locke, A. E. et al. Genetic studies of body mass index yield new insights for obesity biology. Nature 518, 197–206 (2015).
20. Berthoud, H. R., Zheng, H. & Shin, A. C. Food reward in the obese and after weight loss induced by calorie restriction and bariatric surgery. Ann. NY Acad. Sci. 1264, 36–48 (2012).
21. Fulton, S. Appetite and reward. Front. Neuroendocrinol. 31, 85–103 (2010).
22. Schneeberger, M., Gomis, R. & Claret, M. Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance. J. Endocrinol. 220, T25–T46 (2014).
23. Dagher, A. Functional brain imaging of appetite. Trends Endocrinol. Metab. 23, 250–260 (2012).
24. Woods, S. C. The control of food intake: behavioral versus molecular perspectives. Cell Metab. 9, 489–498 (2009).
25. Dietrich, M. O. & Horvath, T. L. Hypothalamic control of energy balance: insights into the role of synaptic plasticity. Trends Neurosci. 36, 65–73 (2013).
26. Stice, E., Figlewicz, D. P., Gosnell, B. A., Levine, A. S. & Pratt, W. E. The contribution of brain reward circuits to the obesity epidemic. Neurosci. Biobehav. Rev. 37, 2047–2058 (2013).
27. Volkow, N. D., Wang, G. J., Tomasi, D. & Baler, R. D. Obesity and addiction: neurobiological overlaps. Obes. Rev. 14, 2–18 (2013).
28. Richard, D., Monge-Roffarello, B., Chechi, K., Labbe, S. M. & Turcotte, E. E. Control and physiological determinants of sympathetically mediated brown adipose tissue thermogenesis. Front. Endocrinol. (Lausanne) 3, 36 (2012).
29. Richard, D. Energy expenditure: a critical determinant of energy balance with key hypothalamic controls. Minerva Endocrinol. 32, 173–183 (2007).
30. Castro, D. C. & Berridge, K. C. Advances in the neurobiological bases for food ‘liking’ versus ‘wanting’. Physiol. Behav. 136, 22–30 (2014).
31. Morrison, S. F., Madden, C. J. & Tupone, D. Central neural regulation of brown adipose tissue thermogenesis and energy expenditure. Cell Metab. 19, 741–756 (2014).
32. Olsen, C. M. Natural rewards, neuroplasticity, and non-drug addictions. Neuropharmacology 61, 1109–1122 (2011).
33. Bartness, T. J., Vaughan, C. H. & Song, C. K. Sympathetic and sensory innervation of brown adipose tissue. Int. J. Obes. (Lond.) 34 (Suppl. 1), S36–S42 (2010).
34. Schwartz, M. W., Woods, S. C., Porte, D. Jr, Seeley, R. J. & Baskin, D. G. Central nervous system control of food intake. Nature 404, 661–671 (2000).
35. Vainik, U., Dagher, A., Dubé, L. & Fellows, L. K. Neurobehavioural correlates of body mass index and eating behaviours in adults: a systematic review. Neurosci. Biobehav. Rev. 37, 279–299 (2013).
36. Veit, R. et al. Reduced cortical thickness associated with visceral fat and BMI. Neuroimage Clin. 6, 307–311 (2014).
37. Cazettes, F., Cohen, J. I., Yau, P. L., Talbot, H. & Convit, A. Obesity-mediated inflammation may damage the brain circuit that regulates food intake. Brain Res. 1373, 101–109 (2011).
38. Goldman, R. L. et al. Executive control circuitry differentiates degree of success in weight loss following gastric-bypass surgery. Obesity (Silver Spring) 21, 2189–2196 (2013).
39. Dietrich, A., Federbusch, M., Grellmann, C., Villringer, A. & Horstmann, A. Body weight status, eating behavior, sensitivity to reward/punishment, and gender: relationships and interdependencies. Front. Psychol. 5, 1073 (2014).
40. Bongers, P. et al. Being impulsive and obese increases susceptibility to speeded detection of high-calorie foods. Health Psychol. 34, 677–685 (2015).
41. Folkvord, F., Anschutz, D. J., Nederkoorn, C., Westerik, H. & Buijzen, M. Impulsivity, “advergames,” and food intake. Pediatrics 133, 1007–1012 (2014).
42. Sutin, A., Ferrucci, L., Zonderman, A. & Terracciano, A. Personality and obesity across the adult life span. J. Pers. Soc. Psychol. 101, 579–592 (2011).
43. Jansen, A. et al. High-restrained eaters only overeat when they are also impulsive. Behav. Res. Ther. 47, 105–110 (2009).
44. Robinson, T. E. & Berridge, K. C. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res. Brain Res. Rev. 18, 247–291 (1993).
45. Berridge, K. C. & Robinson, T. E. Parsing reward. Trends Neurosci. 26, 507–513 (2003).
46. Berridge, K. C., Ho, C. Y., Richard, J. M. & DiFeliceantonio, A. G. The tempted brain eats: pleasure and desire circuits in obesity and eating disorders. Brain Res. 1350, 43–64 (2010).
47. Small, D. M. Taste representation in the human insula. Brain Struct. Funct. 214, 551–561 (2010).
48. King, B. M. The modern obesity epidemic, ancestral hunter-gatherers, and the sensory/reward control of food intake. Am. Psychol. 68, 88–96 (2013).
49. Sominsky, L. & Spencer, S. J. Eating behavior and stress: a pathway to obesity. Front. Psychol. 5, 434 (2014).
50. Gibson, E. L. The psychobiology of comfort eating: implications for neuropharmacological interventions. Behav. Pharmacol. 23, 442–460 (2012).
51. Richard, J. M., Castro, D. C., Difeliceantonio, A. G., Robinson, M. J. & Berridge, K. C. Mapping brain circuits of reward and motivation: in the footsteps of Ann Kelley. Neurosci. Biobehav. Rev. 37, 1919–1931 (2013).
52. Stice, E., Spoor, S., Bohon, C. & Small, D. M. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science 322, 449–452 (2008).
53. Kenny, P. J., Voren, G. & Johnson, P. M. Dopamine D2 receptors and striatopallidal transmission in addiction and obesity. Curr. Opin. Neurobiol. 23, 535–538 (2013).
54. Trifilieff, P. & Martinez, D. Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity. Neuropharmacology 76 (Pt B), 498–509 (2014).
55. Volkow, N. D. et al. Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. NeuroImage 42, 1537–1543 (2008).
56. Volkow, N. D., Wang, G. J., Tomasi, D. & Baler, R. D. The addictive dimensionality of obesity. Biol. Psychiatry 73, 811–818 (2013).
57. Richard, D., Guesdon, B. & Timofeeva, E. The brain endocannabinoid system in the regulation of energy balance. Best Pract Res. Clin. Endocrinol. Metab. 23, 17–32 (2009).
58. Pecina, S. & Smith, K. S. Hedonic and motivational roles of opioids in food reward: implications for overeating disorders. Pharmacol. Biochem. Behav. 97, 34–46 (2010).
59. Cristino, L., Becker, T. & Di Marzo, V. Endocannabinoids and energy homeostasis: an update. Biofactors 40, 389–397 (2014).
60. Bermudez-Silva, F. J., Cardinal, P. & Cota, D. The role of the endocannabinoid system in the neuroendocrine regulation of energy balance. J. Psychopharmacol. 26, 114–124 (2012).
61. Bodnar, R. J. Endogenous opiates and behavior: 2013. Peptides 62, 67–136 (2014).
62. Di Marzo, V. Endocannabinoids: synthesis and degradation. Rev. Physiol. Biochem. Pharmacol. 160, 1–24 (2008).
63. Cota, D., Tschop, M. H., Horvath, T. L. & Levine, A. S. Cannabinoids, opioids and eating behavior: the molecular face of hedonism? Brain Res. Rev. 51, 85–107 (2006).
64. Mahler, S. V., Smith, K. S. & Berridge, K. C. Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances ‘liking’ of a sweet reward. Neuropsychopharmacology 32, 2267–2278 (2007).
65. Castro, D. C. & Berridge, K. C. Opioid hedonic hotspot in nucleus accumbens shell: μ, δ, and κ maps for enhancement of sweetness “liking” and “wanting”. J. Neurosci. 34, 4239–4250 (2014).
66. Pecina, S. & Berridge, K. C. Dopamine or opioid stimulation of nucleus accumbens similarly amplify cue-triggered ‘wanting’ for reward: entire core and medial shell mapped as substrates for PIT enhancement. Eur. J. Neurosci. 37, 1529–1540 (2013).
67. Margolis, E. B., Hjelmstad, G. O., Fujita, W. & Fields, H. L. Direct bidirectional μ-opioid control of midbrain dopamine neurons. J. Neurosci. 34, 14707–14716 (2014).
68. Riegel, A. C. & Lupica, C. R. Independent presynaptic and postsynaptic mechanisms regulate endocannabinoid signaling at multiple synapses in the ventral tegmental area. J. Neurosci. 24, 11070–11078 (2004).
69. Zuberi, A. R., Townsend, L., Patterson, L., Zheng, H. & Berthoud, H. R. Increased adiposity on normal diet, but decreased susceptibility to diet-induced obesity in μ-opioid receptor-deficient mice. Eur. J. Pharmacol. 585, 14–23 (2008).
70. Czyzyk, T. A. et al. Mice lacking δ-opioid receptors resist the development of diet-induced obesity. FASEB J. 26, 3483–3492 (2012).
71. Ravinet Trillou, C., Delgorge, C., Menet, C., Arnone, M. & Soubrie, P. CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int. J. Obes. Relat. Metab. Disord. 28, 640–648 (2004).
72. Grissom, N. M. et al. Obesity at conception programs the opioid system in the offspring brain. Neuropsychopharmacology 39, 801–810 (2014).
73. Coll, A. P. & Yeo, G. S. The hypothalamus and metabolism: integrating signals to control energy and glucose homeostasis. Curr. Opin. Pharmacol. 13, 970–976 (2013).
74. Williams, G. et al. The hypothalamus and the control of energy homeostasis: different circuits, different purposes. Physiol. Behav. 74, 683–701 (2001).
75. Joly-Amado, A. et al. The hypothalamic arcuate nucleus and the control of peripheral substrates. Best Pract. Res. Clin. Endocrinol. Metab. 28, 725–737 (2014).
76. Sainsbury, A. & Zhang, L. Role of the arcuate nucleus of the hypothalamus in regulation of body weight during energy deficit. Mol. Cell. Endocrinol. 316, 109–119 (2010).
77. Ghamari-Langroudi, M., Srisai, D. & Cone, R. D. Multinodal regulation of the arcuate/paraventricular nucleus circuit by leptin. Proc. Natl Acad. Sci. USA 108, 355–360 (2011).
78. Kelley, A. E., Baldo, B. A. & Pratt, W. E. A proposed hypothalamic–thalamic–striatal axis for the integration of energy balance, arousal, and food reward. J. Comp. Neurol. 493, 72–85 (2005).
79. Shah, B. P. et al. MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. Proc. Natl Acad. Sci. USA 111, 13193–13198 (2014).
80. Carter, M. E., Soden, M. E., Zweifel, L. S. & Palmiter, R. D. Genetic identification of a neural circuit that suppresses appetite. Nature 503, 111–114 (2013).
81. Simpson, K. A. & Bloom, S. R. Appetite and hedonism: gut hormones and the brain. Endocrinol. Metab. Clin. North Am. 39, 729–743 (2010).
82. Schwartz, G. J. Brainstem integrative function in the central nervous system control of food intake. Forum Nutr. 63, 141–151 (2010).
83. Blevins, J. E. & Baskin, D. G. Hypothalamic-brainstem circuits controlling eating. Forum Nutr. 63, 133–140 (2010).
84. Hajnal, A., Norgren, R. & Kovacs, P. Parabrachial coding of sapid sucrose: relevance to reward and obesity. Ann. NY Acad. Sci. 1170, 347–364 (2009).
85. Girardet, C. & Butler, A. A. Neural melanocortin receptors in obesity and related metabolic disorders. Biochim. Biophys. Acta 1842, 482–494 (2014).
86. Pandit, R., de Jong, J. W., Vanderschuren, L. J. & Adan, R. A. Neurobiology of overeating and obesity: the role of melanocortins and beyond. Eur. J. Pharmacol. 660, 28–42 (2011).
87. Renquist, B. J., Lippert, R. N., Sebag, J. A., Ellacott, K. L. & Cone, R. D. Physiological roles of the melanocortin MC3 receptor. Eur. J. Pharmacol. 660, 13–20 (2011).
88. Mountjoy, K. G. Distribution and function of melanocortin receptors within the brain. Adv. Exp. Med. Biol. 681, 29–48 (2010).
89. Millington, G. W. The role of proopiomelanocortin (POMC) neurones in feeding behaviour. Nutr. Metab. (Lond.) 4, 18 (2007).
90. Elias, C. F. et al. Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron 21, 1375–1385 (1998).
91. Mercer, A. J., Hentges, S. T., Meshul, C. K. & Low, M. J. Unraveling the central proopiomelanocortin neural circuits. Front. Neurosci. 7, 19 (2013).
92. Challis, B. G. et al. Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY3–36. Proc. Natl Acad. Sci. USA 101, 4695–4700 (2004).
93. Coll, A. P., Farooqi, I. S., Challis, B. G., Yeo, G. S. & O’Rahilly, S. Proopiomelanocortin and energy balance: insights from human and murine genetics. J. Clin. Endocrinol. Metab. 89, 2557–2562 (2004).
94. Schwartz, M. W. et al. Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 46, 2119–2123 (1997).
95. Chen, A. S. et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat. Genet. 26, 97–102 (2000).
96. Huszar, D. et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–141 (1997).
97. Valette, M. et al. Eating behaviour in obese patients with melanocortin-4 receptor mutations: a literature review. Int. J. Obes. (Lond.) 37, 1027–1035 (2013).
98. Hebebrand, J., Hinney, A., Knoll, N., Volckmar, A. L. & Scherag, A. Molecular genetic aspects of weight regulation. Dtsch Arztebl. Int. 110, 338–344 (2013).
99. Ste Marie, L., Miura, G. I., Marsh, D. J., Yagaloff, K. & Palmiter, R. D. A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors. Proc. Natl Acad. Sci. USA 97, 12339–12344 (2000).
100. Chen, A. S. et al. Role of the melanocortin-4 receptor in metabolic rate and food intake in mice. Transgenic Res. 9, 145–154 (2000).
101. Brito, M. N., Brito, N. A., Baro, D. J., Song, C. K. & Bartness, T. J. Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation. Endocrinology 148, 5339–5347 (2007).
102. Butler, A. A. et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 141, 3518–3521 (2000).
103. Sutton, G. M. et al. The melanocortin-3 receptor is required for entrainment to meal intake. J. Neurosci. 28, 12946–12955 (2008).
104. Renquist, B. J. et al. Melanocortin-3 receptor regulates the normal fasting response. Proc. Natl Acad. Sci. USA 109, E1489–E1498 (2012).
105. Koch, M. et al. Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature 519, 45–50 (2015).
106. Cowley, M. A. et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411, 480–484 (2001).
107. Bagnol, D. et al. Anatomy of an endogenous antagonist: relationship between Agouti-related protein and proopiomelanocortin in brain. J. Neurosci. 19, RC26 (1999).
108. Haskell-Luevano, C. & Monck, E. K. Agouti-related protein functions as an inverse agonist at a constitutively active brain melanocortin-4 receptor. Regul. Pept. 99, 1–7 (2001).
109. Ghamari-Langroudi, M. et al. G protein independent coupling of MC4R to Kir7.1 in hypothalamic neurons. Nature 520, 94–98 (2015).
110. Cansell, C., Denis, R. G., Joly-Amado, A., Castel, J. & Luquet, S. Arcuate AgRP neurons and the regulation of energy balance. Front. Endocrinol. (Lausanne) 3, 169 (2012).
111. Rossi, M. et al. A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of alpha-melanocyte stimulating hormone in vivo. Endocrinology 139, 4428–4431 (1998).
112. Asakawa, A. et al. Effects of agouti-related protein, orexin and melanin-concentrating hormone on oxygen consumption in mice. Int. J. Mol. Med. 10, 523–525 (2002).
113. Mizuno, T. M. & Mobbs, C. V. Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Endocrinology 140, 814–817 (1999).
114. Shutter, J. R. et al. Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev. 11, 593–602 (1997).
115. Gropp, E. et al. Agouti-related peptide-expressing neurons are mandatory for feeding. Nat. Neurosci. 8, 1289–1291 (2005).
116. Luquet, S., Perez, F. A., Hnasko, T. S. & Palmiter, R. D. NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science 310, 683–685 (2005).
117. Wu, Q. & Palmiter, R. D. GABAergic signaling by AgRP neurons prevents anorexia via a melanocortin-independent mechanism. Eur. J. Pharmacol. 660, 21–27 (2011).
118. Hahn, T. M., Breininger, J. F., Baskin, D. G. & Schwartz, M. W. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat. Neurosci. 1, 271–272 (1998).
119. Chambers, A. P. & Woods, S. C. The role of neuropeptide Y in energy homeostasis. Handb. Exp. Pharmacol. 209, 23–45 (2012).
120. Giraudo, S. Q., Billington, C. J. & Levine, A. S. Feeding effects of hypothalamic injection of melanocortin 4 receptor ligands. Brain Res. 809, 302–306 (1998).
121. Monge-Roffarello, B. et al. The PVH as a site of CB1-mediated stimulation of thermogenesis by MC4R agonism in male rats. Endocrinology 155, 3448–3458 (2014).
122. Song, C. K. et al. Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295, R417–R428 (2008).
123. Balthasar, N. et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123, 493–505 (2005).
124. Larsen, P. J., Moller, M. & Mikkelsen, J. D. Efferent projections from the periventricular and medial parvicellular subnuclei of the hypothalamic paraventricular nucleus to circumventricular organs of the rat: a Phaseolus vulgaris-leucoagglutinin (PHA-L) tracing study. J. Comp. Neurol. 306, 462–479 (1991).
125. Moga, M. M., Weis, R. P. & Moore, R. Y. Efferent projections of the paraventricular thalamic nucleus in the rat. J. Comp. Neurol. 359, 221–238 (1995).
126. Garfield, A. S. et al. A neural basis for melanocortin-4 receptor-regulated appetite. Nat. Neurosci. 18, 863–871 (2015).
127. King, C. M. & Hentges, S. T. Relative number and distribution of murine hypothalamic proopiomelanocortin neurons innervating distinct target sites. PLoS ONE 6, e25864 (2011).
128. Kishi, T. et al. Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J. Comp. Neurol. 457, 213–235 (2003).
129. Roselli-Rehfuss, L. et al. Identification of a receptor for γ melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc. Natl Acad. Sci. USA 90, 8856–8860 (1993).
130. Yen, H. H. & Roseberry, A. G. Decreased consumption of rewarding sucrose solutions after injection of melanocortins into the ventral tegmental area of rats. Psychopharmacology (Berl.) 232, 285–294 (2015).
131. Lippert, R. N., Ellacott, K. L. & Cone, R. D. Gender-specific roles for the melanocortin-3 receptor in the regulation of the mesolimbic dopamine system in mice. Endocrinology 155, 1718–1727 (2014).
132. Cui, H. & Lutter, M. The expression of MC4Rs in D1R neurons regulates food intake and locomotor sensitization to cocaine. Genes Brain Behav. 12, 658–665 (2013).
133. Zheng, J. Q., Seki, M., Hayakawa, T., Ito, H. & Zyo, K. Descending projections from the paraventricular hypothalamic nucleus to the spinal cord: anterograde tracing study in the rat. Okajimas Folia Anat. Jpn 72, 119–135 (1995).
134. Monge-Roffarello, B. et al. The medial preoptic nucleus as a site of the thermogenic and metabolic actions of melanotan II in male rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 307, R158–R166 (2014).
135. Arens, J. et al. Age-dependent hypothalamic expression of neuropeptides in wild-type and melanocortin-4 receptor-deficient mice. Physiol. Genomics 16, 38–46 (2003).
136. Chao, P. T., Yang, L., Aja, S., Moran, T. H. & Bi, S. Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity. Cell Metab. 13, 573–583 (2011).
137. Kim, K. W. et al. Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus. Proc. Natl Acad. Sci. USA 108, 10673–10678 (2011).
138. Lindberg, D., Chen, P. & Li, C. Conditional viral tracing reveals that steroidogenic factor 1-positive neurons of the dorsomedial subdivision of the ventromedial hypothalamus project to autonomic centers of the hypothalamus and hindbrain. J. Comp. Neurol. 521, 3167–3190 (2013).
139. Bamshad, M., Song, C. K. & Bartness, T. J. CNS origins of the sympathetic nervous system outflow to brown adipose tissue. Am. J. Physiol. 276, R1569–R1578 (1999).
140. Cano, G. et al. Anatomical substrates for the central control of sympathetic outflow to interscapular adipose tissue during cold exposure. J. Comp. Neurol. 460, 303–326 (2003).
141. Majdic, G. et al. Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. Endocrinology 143, 607–614 (2002).
142. Cardinal, P. et al. CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin. Mol. Metab. 3, 705–716 (2014).
143. Kim, K. W. et al. FOXO1 in the ventromedial hypothalamus regulates energy balance. J. Clin. Invest. 122, 2578–2589 (2012).
144. Unger, T. J., Calderon, G. A., Bradley, L. C., Sena-Esteves, M. & Rios, M. Selective deletion of Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. J. Neurosci. 27, 14265–14274 (2007).
145. Caron, A., Baraboi, E. D., Laplante, M. & Richard, D. DEP domain-containing mTOR-interacting protein in the rat brain: Distribution of expression and potential implication. J. Comp. Neurol. 523, 93–107 (2015).
146. Cabanac, M. Regulation and the ponderostat. Int. J. Obes. Relat. Metab. Disord. 25 (Suppl. 5), S7–S12 (2001).
147. Levin, B. E. Central regulation of energy homeostasis intelligent design: how to build the perfect survivor. Obesity (Silver Spring) 14 (Suppl. 5), 192S–196S (2006).
148. Keesey, R. E. & Powley, T. L. Body energy homeostasis. Appetite 51, 442–445 (2008).
149. Friedman, J. M. & Halaas, J. L. Leptin and the regulation of body weight in mammals. Nature 395, 763–770 (1998).
150. Munzberg, H. & Morrison, C. D. Structure, production and signaling of leptin. Metabolism 64, 13–23 (2015).
151. Jovanovic, Z. & Yeo, G. S. Central leptin signalling: Beyond the arcuate nucleus. Auton Neurosci. 156, 8–14 (2010).
152. Perello, M. & Dickson, S. L. Ghrelin signaling on food reward: a salient link between the gut and the mesolimbic system. J. Neuroendocrinol. 27, 424–434 (2015).
153. Kirchner, H., Heppner, K. M. & Tschop, M. H. The role of ghrelin in the control of energy balance. Handb. Exp. Pharmacol. 209, 161–184 (2012).
154. Behary, P. & Miras, A. D. Brain responses to food and weight loss. Exp. Physiol. 99, 1121–1127 (2014).
155. Sumithran, P. et al. Long-term persistence of hormonal adaptations to weight loss. N. Engl. J. Med. 365, 1597–1604 (2011).
156. Rosenbaum, M. & Leibel, R. L. Adaptive thermogenesis in humans. Int. J. Obes. 34, S47–S55 (2010).
157. Tremblay, A., Royer, M. M., Chaput, J. P. & Doucet, E. Adaptive thermogenesis can make a difference in the ability of obese individuals to lose body weight. Int. J. Obes. (Lond.) 37, 759–764 (2013).
158. Blundell, J. E. Perspective on the central control of appetite. Obesity (Silver Spring) 14 (Suppl. 4), 160S–163S (2006).
159. Mimee, A., Smith, P. M. & Ferguson, A. V. Circumventricular organs: targets for integration of circulating fluid and energy balance signals? Physiol. Behav. 121, 96–102 (2013).
160. Balland, E. et al. Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metab. 19, 293–301 (2014).
161. Park, H. K. & Ahima, R. S. Leptin signaling. F1000Prime Rep. 6, 73 (2014).
162. Allison, M. B. & Myers, M. G. Jr. 20 years of leptin: connecting leptin signaling to biological function. J. Endocrinol. 223, T25–T35 (2014).
163. Bouret, S. G., Draper, S. J. & Simerly, R. B. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304, 108–110 (2004).
164. Oswal, A. & Yeo, G. S. The leptin melanocortin pathway and the control of body weight: lessons from human and murine genetics. Obes. Rev. 8, 293–306 (2007).
165. Hakansson, M. L., Hulting, A. L. & Meister, B. Expression of leptin receptor mRNA in the hypothalamic arcuate nucleus—relationship with NPY neurones. Neuroreport 7, 3087–3092 (1996).
166. Cheung, C. C., Clifton, D. K. & Steiner, R. A. Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 138, 4489–4492 (1997).
167. Vong, L. et al. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71, 142–154 (2011).
168. Rezai-Zadeh, K. et al. Leptin receptor neurons in the dorsomedial hypothalamus are key regulators of energy expenditure and body weight, but not food intake. Mol. Metab. 3, 681–693 (2014).
169. Opland, D. et al. Loss of neurotensin receptor-1 disrupts the control of the mesolimbic dopamine system by leptin and promotes hedonic feeding and obesity. Mol. Metab. 2, 423–434 (2013).
170. Hommel, J. D. et al. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 51, 801–810 (2006).
171. Alhadeff, A. L., Hayes, M. R. & Grill, H. J. Leptin receptor signaling in the lateral parabrachial nucleus contributes to the control of food intake. Am. J. Physiol. Regul. Integr. Comp. Physiol. 307, R1338–R1344 (2014).
172. Dubern, B. & Clement, K. Leptin and leptin receptor-related monogenic obesity. Biochimie 94, 2111–2115 (2012).
173. Farooqi, I. S. et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N. Engl. J. Med. 341, 879–884 (1999).
174. Halaas, J. L. et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269, 543–546 (1995).
175. Matochik, J. A. et al. Effect of leptin replacement on brain structure in genetically leptin-deficient adults. J. Clin. Endocrinol. Metab. 90, 2851–2854 (2005).
176. Farooqi, I. S. et al. Leptin regulates striatal regions and human eating behavior. Science 317, 1355 (2007).
177. Heymsfield, S. B. et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282, 1568–1575 (1999).
178. Knight, Z. A., Hannan, K. S., Greenberg, M. L. & Friedman, J. M. Hyperleptinemia is required for the development of leptin resistance. PLoS ONE 5, e11376 (2010).
179. Bjorbaek, C. Central leptin receptor action and resistance in obesity. J. Investig. Med. 57, 789–794 (2009).
180. Myers, M. G., Jr., Leibel, R. L., Seeley, R. J. & Schwartz, M. W. Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol. Metab. 21, 643–651 (2010).
181. Mark, A. L. Selective leptin resistance revisited. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305, R566–R581 (2013).
182. Enriori, P. J., Sinnayah, P., Simonds, S. E., Garcia Rudaz, C. & Cowley, M. A. Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown adipose tissue in spite of systemic leptin resistance. J. Neurosci. 31, 12189–12197 (2011).
183. Field, B. C., Chaudhri, O. B. & Bloom, S. R. Bowels control brain: gut hormones and obesity. Nat. Rev. Endocrinol. 6, 444–453 (2010).
184. Sato, T. et al. Structure, regulation and function of ghrelin. J. Biochem. 151, 119–128 (2012).
185. Wortley, K. E. et al. Absence of ghrelin protects against early-onset obesity. J. Clin. Invest. 115, 3573–3578 (2005).
186. Zigman, J. M. et al. Mice lacking ghrelin receptors resist the development of diet-induced obesity. J. Clin. Invest. 115, 3564–3572 (2005).
187. Mason, B. L., Wang, Q. & Zigman, J. M. The central nervous system sites mediating the orexigenic actions of ghrelin. Annu. Rev. Physiol. 76, 519–533 (2014).
188. Cabral, A., Valdivia, S., Fernandez, G., Reynaldo, M. & Perello, M. Divergent neuronal circuitries underlying acute orexigenic effects of peripheral or central ghrelin: critical role of brain accessibility. J. Neuroendocrinol. 26, 542–554 (2014).
189. Wang, Q. et al. Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin. Mol. Metab. 3, 64–72 (2014).
190. Malik, S., McGlone, F., Bedrossian, D. & Dagher, A. Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metab. 7, 400–409 (2008).
191. Haissaguerre, M., Saucisse, N. & Cota, D. Influence of mTOR in energy and metabolic homeostasis. Mol. Cell. Endocrinol. 397, 67–77 (2014).
192. Woods, S. C., Seeley, R. J. & Cota, D. Regulation of food intake through hypothalamic signaling networks involving mTOR. Annu. Rev. Nutr. 28, 295–311 (2008).
193. Laplante, M. & Sabatini, D. M. mTOR signaling in growth control and disease. Cell 149, 274–293 (2012).
194. Gulati, P. & Thomas, G. Nutrient sensing in the mTOR/S6K1 signalling pathway. Biochem. Soc. Trans. 35, 236–238 (2007).
195. Cota, D. et al. Hypothalamic mTOR signaling regulates food intake. Science 312, 927–930 (2006).
196. Harlan, S. M., Guo, D. F., Morgan, D. A., Fernandes-Santos, C. & Rahmouni, K. Hypothalamic mTORC1 signaling controls sympathetic nerve activity and arterial pressure and mediates leptin effects. Cell Metab. 17, 599–606 (2013).
197. Stevanovic, D. et al. Ghrelin-induced food intake and adiposity depend on central mTORC1/S6K1 signaling. Mol. Cell Endocrinol. 381, 280–290 (2013).
198. Kocalis, H. E. et al. Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis. Mol. Metab. 3, 394–407 (2014).
199. Hay, N. Interplay between FOXO, TOR, and Akt. Biochim. Biophys. Acta 1813, 1965–1970 (2011).
200. Sasaki, T. & Kitamura, T. Roles of FoxO1 and Sirt1 in the central regulation of food intake. Endocr. J. 57, 939–946 (2010).
201. Peterson, T. R. et al. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell 137, 873–886 (2009).
202. Laplante, M. et al. DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated with obesity. Cell Metab. 16, 202–212 (2012).
203. Cannon, B. & Nedergaard, J. Brown adipose tissue: function and physiological significance. Physiol. Rev. 84, 277–359 (2004).
204. Enerback, S. et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387, 90–94 (1997).
205. Meyer, C. W. et al. Adaptive thermogenesis and thermal conductance in wild-type and UCP1-KO mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299, R1396–R1406 (2010).
206. Nicholls, D. G. & Locke, R. M. Thermogenic mechanisms in brown fat. Physiol. Rev. 64, 1–64 (1984).
207. Labbe, S. M. et al. In vivo measurement of energy substrate contribution to cold-induced brown adipose tissue thermogenesis. FASEB J. 29, 2046–2058 (2015).
208. Rosenwald, M. & Wolfrum, C. The origin and definition of brite versus white and classical brown adipocytes. Adipocyte 3, 4–9 (2014).
209. Harms, M. & Seale, P. Brown and beige fat: development, function and therapeutic potential. Nat. Med. 19, 1252–1263 (2013).
210. Bordicchia, M. et al. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J. Clin. Invest. 122, 1022–1036 (2012).
211. Fisher, F. M. et al. FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Genes Dev. 26, 271–281 (2012).
212. Lee, P. et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 19, 302–309 (2014).
213. Tseng, Y. H. et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454, 1000–1004 (2008).
214. Whittle, A. J. et al. BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell 149, 871–885 (2012).
215. Nedergaard, J., Bengtsson, T. & Cannon, B. Unexpected evidence for active brown adipose tissue in adult humans. Am. J. Physiol. Endocrinol. Metab. 293, E444–E452 (2007).
216. Cypess, A. M. et al. Identification and importance of brown adipose tissue in adult humans. N. Engl. J. Med. 360, 1509–1517 (2009).
217. Virtanen, K. A. et al. Functional brown adipose tissue in healthy adults. N. Engl. J. Med. 360, 1518–1525 (2009).
218. Zingaretti, M. C. et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 23, 3113–3120 (2009).
219. Ouellet, V. et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J. Clin. Invest. 122, 545–552 (2012).
220. Ouellet, V. et al. Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F FDG detected BAT in humans. J. Clin. Endocrinol. Metab. 96, 192–199 (2011).
221. van Marken Lichtenbelt, W. D. et al. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 360, 1500–1508 (2009).
222. Blondin, D. P. et al. Increased brown adipose tissue oxidative capacity in cold-acclimated humans. J. Clin. Endocrinol. Metab. 99, E438–E446 (2014).
223. van der Lans, A. A. et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J. Clin. Invest. 123, 3395–3403 (2013).
224. Yoneshiro, T. et al. Recruited brown adipose tissue as an antiobesity agent in humans. J. Clin. Invest. 123, 3404–3408 (2013).
225. Cypess, A. M. et al. Activation of human brown adipose tissue by a β3-adrenergic receptor agonist. Cell Metab. 21, 33–38 (2015).
226. Lowell, B. B. et al. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366, 740–742 (1993).
227. Feldmann, H. M., Golozoubova, V., Cannon, B. & Nedergaard, J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 9, 203–209 (2009).
228. Richard, D. & Picard, F. Brown fat biology and thermogenesis. Front. Biosci. 16, 1233–1260 (2011).
229. Drubach, L. A. et al. Pediatric brown adipose tissue: detection, epidemiology, and differences from adults. J. Pediatr. 159, 939–944 (2011).
230. Wang, Q. et al. Brown adipose tissue in humans is activated by elevated plasma catecholamines levels and is inversely related to central obesity. PLoS ONE 6, e21006 (2011).
231. Cypess, A. M., Haft, C. R., Laughlin, M. R. & Hu, H. H. Brown fat in humans: consensus points and experimental guidelines. Cell Metab. 20, 408–415 (2014).
232. Chechi, K., Nedergaard, J. & Richard, D. Brown adipose tissue as an anti-obesity tissue in humans. Obes. Rev. 15, 92–106 (2014).
233. Lidell, M. E., Betz, M. J. & Enerback, S. Brown adipose tissue and its therapeutic potential. J. Intern. Med. 276, 364–377 (2014).
234. Whittle, A., Relat-Pardo, J. & Vidal-Puig, A. Pharmacological strategies for targeting BAT thermogenesis. Trends Pharmacol. Sci. 34, 347–355 (2013).

 

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