Fatty acid-induced astrocyte ketone production and the control of food intake

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 310, Issue 11, 2016, Pages R1186-R1192

  Le Foll, Christelle ^a   Levin, Barry E ^b  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b RUTGERS UNIVERSITY   (United States)

Author keywords

Astrocytes; Feeding; Hypothalamus; Ketone bodies; Metabolic sensing

Indexed keywords

ADENOSINE TRIPHOSPHATE; CD36 ANTIGEN; FATTY ACID; KETONE BODY; LEPTIN; REACTIVE OXYGEN METABOLITE;

ASTROCYTE; CALORIC INTAKE; DIET INDUCED OBESITY; FATTY ACID OXIDATION; FOOD INTAKE; KETOGENESIS; LIPID DIET; LOW FAT DIET; METABOLIC REGULATION; NONHUMAN; PRIORITY JOURNAL; REVIEW; ZONA INCERTA; APPETITE; BIOLOGICAL MODEL; EATING; HYPOTHALAMUS VENTROMEDIAL NUCLEUS; METABOLISM; NERVE CELL; PHYSIOLOGY;

APPETITE; APPETITE REGULATION; ASTROCYTES; DIET, HIGH-FAT; EATING; FATTY ACIDS; KETONE BODIES; MODELS, BIOLOGICAL; NEURONS; VENTROMEDIAL HYPOTHALAMIC NUCLEUS;

EID: 84984799822     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.00113.2016     Document Type: Review

References (108)

1. Abbott NJ, Revest PA, Romero IA. Astrocyte-endothelial interaction: physiology and pathology. Neuropathol Appl Neurobiol 18: 424-433, 1992.
2. Aja S, Landree LE, Kleman AM, Medghalchi SM, Vadlamudi A, McFadden JM, Aplasca A, Hyun J, Plummer E, Daniels K, Kemm M, Townsend CA, Thupari JN, Kuhajda FP, Moran TH, Ronnett GV. Pharmacological stimulation of brain carnitinepalmitoyl-transferase-1 decreases food Intake and body weight. Am J Physiol Regul Integr Comp Physiol 294: R352-R361, 2008.
3. Aja S, McFadden J, Aplasca A, Plummer E, Hyun J, Medghalchi SM, Vadlamudi A, Thupari JN, Townsend CA, Kuhajda FP, Moran TH, Ronnett GV. Intracerebroventricular administration of either C89b, a stimulator of carnitinepalmitoyl-transferase-1 (CPT-1s), or cerulenin, an inhibitor of fatty acid synthase (FASi), reduces food intake and body weight in mice. Appetite 46: 338, 2006.
4. Anand BK, Chhina GS, Sharma KN, Dua S, Singh B. Activity of single neurons in the hypothalamus feeding centers: effect of glucose. Am J Physiol 207: 1146-1154, 1964.
5. Araque A, Carmignoto G, Haydon PG, Oliet SH, Robitaille R, Volterra A. Gliotransmitters travel in time and space. Neuron 81: 728-739, 2014.
6. Auestad N, Korsak RA, Morrow JW, Edmond J. Fatty acid oxidation and ketogenesis by astrocytes in primary culture. J Neurochem 56: 1376-1386, 1991.
7. Azari EK, Ramachandran D, Weibel S, Arnold M, Romano A, Gaetani S, Langhans W, Mansouri A. Vagal afferents are not necessary for the satiety effect of the gut lipid messenger oleoylethanolamide. Am J Physiol Regul Integr Comp Physiol 307: R167-R178, 2014.
8. Baillie AG, Coburn CT, Abumrad NA. Reversible binding of longchain fatty acids to purified FAT, the adipose CD36 homolog. J Membr Biol 153: 75-81, 1996.
9. Belanger M, Allaman I, Magistretti PJ. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14: 724-738, 2011.
10. Blazquez C, Sanchez C, Daza A, Galve-Roperh I, Guzman M. The stimulation of ketogenesis by cannabinoids in cultured astrocytes defines carnitine palmitoyltransferase I as a new ceramide-activated enzyme. J Neurochem 72: 1759-1768, 1999.
11. Blouet C, Schwartz GJ. Hypothalamic nutrient sensing in the control of energy homeostasis. Behav Brain Res 209: 1-12, 2010.
12. Bouret SG, Gorski JN, Patterson CM, Chen S, Levin BE, Simerly RB. Hypothalamic neural projections are permanently disrupted in dietinduced obese rats. Cell Metab 7: 179-185, 2008.
13. Bray GA, Paeratakul S, Popkin BM. Dietary fat and obesity: a review of animal, clinical and epidemiological studies. Physiol Behav 83: 549-555, 2004.
14. Brekke E, Morken TS, Sonnewald U. Glucose metabolism and astrocyte-neuron interactions in the neonatal brain. Neurochem Int 82: 33-41, 2015.
15. Campfield A, Brandon P, Smith F. On-line continuous measurement of blood glucose and meal pattern in free feeding rats: The role of glucose in meal initiation. Brain Res Bull 14: 605-616, 1985.
16. Carneiro L, Geller S, Fioramonti X, Hebert A, Repond C, Leloup C, Pellerin L. Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice. Am J Physiol Endocrinol Metab 310: E103-E115, 2016.
17. Chen X, Ge Y, Jiang Z, Liu C, Depoorter I, Peeters T. Effects of ghrelin on hypothalamic glucose responding neurons in rats. Brain Res 1055: 131-136, 2005.
18. Clegg DJ, Wortman MD, Benoit SC, McOsker CC, Seeley RJ. Comparison of central and peripheral administration of C75 on food intake, body weight, and conditioned taste aversion. Diabetes 51: 3196-3201, 2002.
19. Cruciani-Guglielmacci C, Marsollier N, Guissard C, Lorsignol A, Penicaud L, Magnan C. Short-term increase in brain FFA reduces food intake. Diabetes 57: A84, 2008.
20. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin NA 88: 787-835, ix, 2004.
21. Dunn-Meynell AA, Routh VH, Kang L, Gaspers L, Levin BE. Glucokinase is the likely mediator of glucosensing in both glucose excited and glucose inhibited central neurons. Diabetes 51: 2056-2065, 2002.
22. Dunn-Meynell AA, Sanders NM, Compton D, Becker TC, Eiki J, Zhang BB, Levin BE. Relationship among brain and blood glucose levels and spontaneous and glucoprivic feeding. J Neurosci 29: 7015-7022, 2009.
23. Edmond J. Energy metabolism in developing brain cells. Can J Physiol Pharmacol 70 Suppl: S118-S129, 1992.
24. Edmond J, Higa TA, Korsak RA, Bergner EA, Lee WN. Fatty acid transport and utilization for the developing brain. J Neurochem 70: 1227-1234, 1998.
25. Edmond J, Robbins RA, Bergstrom JD, Cole RA, de Vellis J. Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J Neurosci Res 18: 551-561, 1987.
26. El-Yassimi A, Hichami A, Besnard P, Khan NA. Linoleic acid induces calcium signaling, Src kinase phosphorylation, and neurotransmitter release in mouse CD36-positive gustatory cells. J Biol Chem 283: 12,949–-12,959, 2008.
27. Ericson U, Hellstrand S, Brunkwall L, Schulz CA, Sonestedt E, Wallstrom P, Gullberg B, Wirfalt E, Orho-Melander M. Food sources of fat may clarify the inconsistent role of dietary fat intake for incidence of type 2 diabetes. Am J Clin Nutr 101: 1065-1080, 2015.
28. Escartin C, Pierre K, Colin A, Brouillet E, Delzescaux T, Guillermier M, Dhenain M, Deglon N, Hantraye P, Pellerin L, Bonvento G. Activation of astrocytes by CNTF induces metabolic plasticity and increases resistance to metabolic insults. J Neurosci 27: 7094-7104, 2007.
29. + channel-independent mechanism is involved in glucoseexcited neurons of mouse arcuate nucleus. Diabetes 53: 2767-2775, 2004.
30. Golay A, Bobbioni E. The role of dietary fat in obesity. Int J Obes Relat Metab Disord 21 Suppl 3: S2-S11, 1997.
31. Gorski JN, Dunn-Meynell AA, Hartman TG, Levin BE. Postnatal environment overrides genetic and prenatal factors influencing offspring obesity and insulin resistance. Am J Physiol Regul Integr Comp Physiol 291: R768-R778, 2006.
32. Gorski JN, Dunn-Meynell AA, Levin BE. Maternal obesity increases hypothalamic leptin receptor expression and sensitivity in juvenile obesity-prone rats. Am J Physiol Regul Integr Comp Physiol 292: R1782-R1791, 2007.
33. Guzman M, Blazquez C. Ketone body synthesis in the brain: possible neuroprotective effects. Prostaglandins Leukot Essent Fatty Acids 70: 287-292, 2004.
34. Hartmann P, Ramseier A, Gudat F, Mihatsch MJ, Polasek W. [Normal weight of the brain in adults in relation to age, sex, body height and weight]. Der Pathologe 15: 165-170, 1994.
35. Hawkins RA, Biebuyck JF. Ketone bodies are selectively used by individual brain regions. Science 205: 325-327, 1979.
36. Hegardt FG. Regulation of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene expression in liver and intestine from the rat. Biochem Soc Trans 23: 486-490, 1995.
37. Hegardt FG. Transcriptional regulation of mitochondrial HMG-CoA synthase in the control of ketogenesis. Biochimie 80: 803-806, 1998.
38. Irani BG, Le Foll C, Dunn-Meynell A, Levin BE. Effects of leptin on rat ventromedial hypothalamic neurons. Endocrinology 149: 5146-5154, 2008.
39. Irani BG, Le Foll C, Dunn-Meynell AA, Levin BE. Ventromedial nucleus neurons are less sensitive to leptin excitation in rats bred to develop diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 296: R521-R527, 2009.
40. Jo YH, Su Y, Gutierrez-Juarez R, Chua S Jr. Oleic acid directly regulates POMC neuron excitability in the hypothalamus. J Neurophysiol 101: 2305-2316, 2009.
41. Kang L, Dunn-Meynell AA, Routh VH, Gaspers LD, Nagata Y, Nishimura T, Eiki J, Zhang BB, Levin BE. Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing. Diabetes 55: 412-420, 2006.
42. Kang L, Routh VH, Kuzhikandathil EV, Gaspers L, Levin BE. Physiological and molecular characteristics of rat hypothalamic ventromedial nucleus glucosensing neurons. Diabetes 53: 549-559, 2004.
43. Karimian Azari E, Leitner C, Jaggi T, Langhans W, Mansouri A. Possible role of intestinal fatty acid oxidation in the eating-inhibitory effect of the PPAR-agonist Wy-14643 in high-fat diet fed rats. PloS One 8: e74869, 2013.
44. Lam CK, Chari M, Rutter GA, Lam TK. Hypothalamic nutrient sensing activates a forebrain-hindbrain neuronal circuit to regulate glucose production in vivo. Diabetes 60: 107-113, 2011.
45. Lam TK, Pocai A, Gutierrez-Juarez R, Obici S, Bryan J, Aguilar-Bryan L, Schwartz GJ, Rossetti L. Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis. Nat Med 11: 320-327, 2005.
46. Lamy CM, Sanno H, Labouebe G, Picard A, Magnan C, Chatton JY, Thorens B. Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion. Cell Metab 19: 527-538, 2014.
47. Le Foll C, Dunn-Meynell A, Levin BE. Role of FAT/CD36 in fatty acid sensing, energy and glucose homeostasis regulation in DIO and DR rats. Am J Physiol Regul Integr Comp Physiol 308: R188-R198, 2015.
48. Le Foll C, Dunn-Meynell A, Musatov S, Magnan C, Levin BE. FAT/CD36: a major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice. Diabetes 62: 2709-2716, 2013.
49. Le Foll C, Dunn-Meynell AA, Miziorko HM, Levin BE. Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids. Diabetes 63: 1259-1269, 2014.
50. Le Foll C, Dunn-Meynell AA, Miziorko HM, Levin BE. Role of VMH ketone bodies in adjusting caloric intake to increased dietary fat content in DIO and DR rats. Am J Physiol Regul Integr Comp Physiol 308: R872-R878, 2015.
51. Le Foll C, Irani BG, Magnan C, Dunn-Meynell AA, Levin BE. Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing. Am J Physiol Regul Integr Comp Physiol 297: R655-R664, 2009.
52. Le Foll C, Irani BG, Magnan C, Dunn-Meynell AA, Levin BE. Effects of maternal genotype and diet on offspring glucose and fatty acid sensing ventromedial hypothalamic nucleus neurons. Am J Physiol Regul Integr Comp Physiol 297: R1351-R1357, 2009.
53. Levin BE. Metabolic sensors: viewing glucosensing neurons from a broader perspective. Physiol Behav 76: 397-401, 2002.
54. Levin BE, Dunn-Meynell AA. Defense of body weight against chronic caloric restriction in obesity-prone and-resistant rats. Am J Physiol Regul Integr Comp Physiol 278: R231-R237, 2000.
55. Levin BE, and Dunn-Meynell AA. Reduced central leptin sensitivity in rats with diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 283: R941-R948, 2002.
56. Levin BE, Dunn-Meynell AA, Balkan B, Keesey RE. Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol 273: R725-R730, 1997.
57. Levin BE, Dunn-Meynell AA, Ricci MR, Cummings DE. Abnormalities of leptin and ghrelin regulation in obesity-prone juvenile rats. Am J Physiol Endocrinol Metab 285: E949-E957, 2003.
58. Levin BE, Dunn-Meynell AA, Routh VH. Brain glucose sensing and body energy homeostasis: role in obesity and diabetes. Am J Physiol Regul Integr Comp Physiol 276: R1223-R1231, 1999.
59. Levin BE, Dunn-Meynell AA, Routh VH. Brain glucosensing and the KATP channel. Nat Neurosci 4: 459-460, 2001.
60. Levin BE, Kang L, Sanders NM, Dunn-Meynell AA. Role of neuronal glucosensing in the regulation of energy homeostasis. Diabetes 55 Suppl 2: S122-S130, 2006.
61. Levin BE, Keesey RE. Defense of differing body weight set-points in diet-induced obese and resistant rats. Am J Physiol Regul Integr Comp Physiol 274: R412-R419, 1998.
62. Levin BE, Magnan C, Dunn-Meynell A, Le Foll C. Metabolic sensing and the brain: who, what, where, and how? Endocrinology 152: 2552-2557, 2011.
63. Levin BE, Routh VH, Kang L, Sanders NM, Dunn-Meynell AA. Neuronal glucosensing: what do we know after 50 years? Diabetes 53: 2521-2528, 2004.
64. Liu B, Niu L, Shen MZ, Gao L, Wang C, Li J, Song LJ, Tao Y, Meng Q, Yang QL, Gao GD, Zhang H. Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy. Mol Neurobiol 50: 327-338, 2014.
65. Magistretti PJ, Pellerin L. Astrocytes couple synaptic activity to glucose utilization in the brain. News Physiol Sci 14: 177-182, 1999.
66. Mayer J. Glucostatic mechanism of regulation of food intake. N Engl J Med 249: 13-16, 1953.
67. Mayer J. Regulation of energy intake and the body weight: the glucostatic theory and lipostatic hypothesis. Ann NY Acad Sci 63: 15-43, 1955.
68. McGarry JD, Foster DW. Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem 49: 395-420, 1980.
69. McKenna MC. Substrate competition studies demonstrate oxidative metabolism of glucose, glutamate, glutamine, lactate and 3-hydroxybutyrate in cortical astrocytes from rat brain. Neurochem Res 37: 2613-2626, 2012.
70. McNay EC, Gold PE. Extracellular glucose concentrations in the rat hippocampus measured by zero-net-flux: effects of microdialysis flow rate, strain, and age. J Neurochem 72: 785-790, 1999.
71. Melanson KJ, Westerterp-Plantenga MS, Campfield LA, Saris WH. Blood glucose and meal patterns in time-blinded males, after aspartame, carbohydrate, and fat consumption, in relation to sweetness perception. Br J Nutr 82: 437-446, 1999.
72. Migrenne S, Cruciani-Guglielmacci C, Kang L, Wang R, Rouch C, Lefevre AL, Ktorza A, Routh VH, Levin BE, Magnan C. Fatty acid signaling in the hypothalamus and the neural control of insulin secretion. Diabetes 55 Suppl 2: S139-S144, 2006.
73. Migrenne S, Magnan C, Cruciani-Guglielmacci C. Fatty acid sensing and nervous control of energy homeostasis. Diabetes Metab 33: 177-182, 2007.
74. Moore MC, Coate KC, Winnick JJ, An Z, Cherrington AD. Regulation of hepatic glucose uptake and storage in vivo. Adv Nutr 3: 286-294, 2012.
75. Moulle VS, Le Foll C, Philippe E, Kassis N, Rouch C, Marsollier N, Bui LC, Guissard C, Dairou J, Lorsignol A, Penicaud L, Levin BE, Cruciani-Guglielmacci C, Magnan C. Fatty acid transporter CD36 mediates hypothalamic effect of fatty acids on food intake in rats. PloS One 8: e74021, 2013.
76. Munsters MJ, Saris WH. Body weight regulation and obesity: dietary strategies to improve the metabolic profile. Annu Rev Food Science Technol 5: 39-51, 2014.
77. Obici S, Feng Z, Arduini A, Conti R, Rossetti L. Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med 9: 756-761, 2003.
78. Obici S, Feng Z, Morgan K, Stein D, Karkanias G, Rossetti L. Central administration of oleic acid inhibits glucose production and food intake. Diabetes 51: 271-275, 2002.
79. Oomura Y. Glucose as a regulator of neuronal activity. In: Advances in Metabolic Disorders, edited by Szabo AJ. New York: Academic Press, 1983, p. 31-65.
80. Oomura Y, Kimura K, Ooyama H, Maeno T, Iki M, Kuniyoshi M. Reciprocal activities of the ventromedial and lateral hypothalamic areas of cats. Science 143: 484-485, 1964.
81. Oomura Y, Nakamura T, Sugimori M, Yamada Y. Effect of free fatty acid on the rat lateral hypothalamic neurons. Physiol Behav 14: 483-486, 1975.
82. Oomura Y, Ono T, Ooyama H, Wayner MJ. Glucose and osmosensitive neurons of the rat hypothalamus. Nature 222: 282-284, 1969.
83. Park S, Kim da S, Daily JW. Central infusion of ketone bodies modulates body weight and hepatic insulin sensitivity by modifying hypothalamic leptin and insulin signaling pathways in type 2 diabetic rats. Brain Res 1401: 95-103, 2011.
84. Pellerin L, Magistretti PJ. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci 91: 10625-10629, 1994.
85. Pellerin L, Magistretti PJ. Sweet sixteen for ANLS. J Cereb Blood Flow Metab 32: 1152-1166, 2012.
86. Pellerin L, Pellegri G, Bittar PG, Charnay Y, Bouras C, Martin JL, Stella N, Magistretti PJ. Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Dev Neurosci 20: 291-299, 1998.
87. Perea G, Navarrete M, Araque A. Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32: 421-431, 2009.
88. Perea G, Sur M, Araque A. Neuron-glia networks: integral gear of brain function. Front Cell Neurosci 8: 378, 2014.
89. Peters A, Schweiger U, Pellerin L, Hubold C, Oltmanns KM, Conrad M, Schultes B, Born J, Fehm HL. The selfish brain: competition for energy resources. Neurosci Biobehav Rev 28: 143-180, 2004.
90. Pocai A, Lam TK, Obici S, Gutierrez-Juarez R, Muse ED, Arduini A, Rossetti L. Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats. J Clin Invest 116: 1081-1091, 2006.
91. Ricci MR, Levin BE. Ontogeny of diet-induced obesity in selectivelybred Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol 285: R610-R618, 2003.
92. + channel in the ventromedial hypothalamic nucleus. Brain Res 778: 107-119, 1997.
93. Routh VH, Song Z, Liu X. The role of glucosensing neurons in the detection of hypoglycemia. Diabetes Technol Ther 6: 413-421, 2004.
94. Rui L. Energy metabolism in the liver. Compr Physiol 4: 177-197, 2014.
95. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 404: 661-671, 2000.
96. Sharabi K, Tavares CD, Rines AK, Puigserver P. Molecular pathophysiology of hepatic glucose production. Mol Aspects Med 46: 21-33, 2015.
97. Silver IA, Erecinska M. Glucose-induced intracellular ion changes in sugar-sensitive hypothalamic neurons. J Neurophysiol 79: 1733-1745, 1998.
98. Simpson JL. Genetics of diabetes mellitus (DM) and anomalies in offspring of diabetic mothers. Semin Perinatol 2: 383-394, 1978.
99. Sokoloff L, Reivich M, Kennedy C, DesRosiers MH, Patlak CS, Pettigrew O, Sakaruda O, Shinohara M. The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 23: 897-916, 1977.
100. Song Z, Levin BE, McArdle JJ, Bakhos N, Routh VH. Convergence of pre-and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus (VMN). Diabetes 50: 2673-2681, 2001.
101. Song Z, Routh VH. Differential effects of glucose and lactate on glucosensing neurons in the ventromedial hypothalamic nucleus. Diabetes 54: 15-22, 2005.
102. Spanswick D, Smith MA, Groppi VE, Logan SD, Ashford ML. Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature 390: 521-525, 1997.
103. + channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci 3: 757-758, 2000.
104. Tsacopoulos M, Magistretti PJ. Metabolic coupling between glia and neurons. J Neurosci 16: 877-885, 1996.
105. Wang R, Cruciani-Guglielmacci C, Migrenne S, Magnan C, Cotero VE, Routh VH. Effects of oleic acid on distinct populations of neurons in the hypothalamic arcuate nucleus are dependent on extracellular glucose levels. J Neurophysiol 95: 1491-1498, 2006.
106. Wang R, Liu X, Hentges ST, Dunn-Meynell AA, Levin BE, Wang W, Routh VH. The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides. Diabetes 53: 1959-1965, 2004.
107. Woods SC, Lotter EC, McKay LD, Porte D Jr. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 282: 503-505, 1979.
108. Yi CX, Habegger KM, Chowen JA, Stern J, Tschop MH. A role for astrocytes in the central control of metabolism. Neuroendocrinology 93: 143-149, 2011.