Lipid sensing and insulin resistance in the brain

Cell Metabolism

Volumn 15, Issue 5, 2012, Pages 646-655

  Yue, Jessica T Y ^a,b   Lam, Tony K T ^a,b,c  

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE (POTASSIUM); ADENOSINE TRIPHOSPHATE SENSITIVE POTASSIUM CHANNEL; CARNITINE PALMITOYLTRANSFERASE I; INSULIN RECEPTOR; LIPID; LONG CHAIN FATTY ACID COENZYME A LIGASE; MALONYL COENZYME A; PROTEIN KINASE C; STAT3 PROTEIN;

BRAIN; CHEMICAL ANALYSIS; FOOD INTAKE; GLUCONEOGENESIS; HOMEOSTASIS; HUMAN; HYPOTHALAMUS; INSULIN RESISTANCE; LIPID ANALYSIS; LIPID DIET; MOLECULAR MECHANICS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PRIORITY JOURNAL; REVIEW; RHOMBENCEPHALON; SIGNAL TRANSDUCTION; VENTRAL TEGMENTUM; ZONA INCERTA;

ANIMALS; HUMANS; HYPOTHALAMUS; INSULIN; INSULIN RESISTANCE; LIPID METABOLISM; MICE; MICE, KNOCKOUT; RATS; SIGNAL TRANSDUCTION;

EID: 84860459626     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2012.01.013     Document Type: Review

References (111)

1. G.C. Agarwala, R.K. Mittal, S.K. Bapat, and U.R. Bhardwaj Effect of centrally administered insulin on blood glucose levels in dogs Indian J. Physiol. Pharmacol. 21 1977 11 18 (Pubitemid 8082308)
2. M.K. Badman, and J.S. Flier The gut and energy balance: visceral allies in the obesity wars Science 307 2005 1909 1914 (Pubitemid 40404693)
3. J.G. Barrera, D.A. Sandoval, D.A. D'Alessio, and R.J. Seeley GLP-1 and energy balance: an integrated model of short-term and long-term control Nat Rev Endocrinol 7 2011 507 516
4. B.F. Belgardt, and J.C. Brüning CNS leptin and insulin action in the control of energy homeostasis Ann. N Y Acad. Sci. 1212 2010 97 113
5. B.F. Belgardt, J. Mauer, F.T. Wunderlich, M.B. Ernst, M. Pal, G. Spohn, H.S. Brönneke, S. Brodesser, B. Hampel, A.C. Schauss, and J.C. Brüning Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism Proc. Natl. Acad. Sci. USA 107 2010 6028 6033
6. S.C. Benoit, C.J. Kemp, C.F. Elias, W. Abplanalp, J.P. Herman, S. Migrenne, A.L. Lefevre, C. Cruciani-Guglielmacci, C. Magnan, and F. Yu Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents J. Clin. Invest. 119 2009 2577 2589
7. R.N. Bergman Orchestration of glucose homeostasis: from a small acorn to the California oak Diabetes 56 2007 1489 1501 (Pubitemid 46842592)
8. O. Bezy, T.T. Tran, J. Pihlajamäki, R. Suzuki, B. Emanuelli, J. Winnay, M.A. Mori, J. Haas, S.B. Biddinger, and M. Leitges PKCδ regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans J. Clin. Invest. 121 2011 2504 2517
9. P.G. Bittar, Y. Charnay, L. Pellerin, C. Bouras, and P.J. Magistretti Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain J. Cereb. Blood Flow Metab. 16 1996 1079 1089 (Pubitemid 26365358)
10. C. Blouet, Y.H. Jo, X. Li, and G.J. Schwartz Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit J. Neurosci. 29 2009 8302 8311
11. G. Boden, P. She, M. Mozzoli, P. Cheung, K. Gumireddy, P. Reddy, X. Xiang, Z. Luo, and N. Ruderman Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver Diabetes 54 2005 3458 3465 (Pubitemid 43334336)
12. J.C. Brüning, D. Gautam, D.J. Burks, J. Gillette, M. Schubert, P.C. Orban, R. Klein, W. Krone, D. Müller-Wieland, and C.R. Kahn Role of brain insulin receptor in control of body weight and reproduction Science 289 2000 2122 2125
13. C. Cabou, C. Vachoux, G. Campistron, D.J. Drucker, and R. Burcelin Brain GLP-1 signaling regulates femoral artery blood flow and insulin sensitivity through hypothalamic PKC-δ Diabetes 60 2011 2245 2256
14. L. Caspi, P.Y. Wang, and T.K. Lam A balance of lipid-sensing mechanisms in the brain and liver Cell Metab. 6 2007 99 104 (Pubitemid 47163623)
15. M. Cesquini, G.R. Stoppa, P.O. Prada, A.S. Torsoni, T. Romanatto, A. Souza, M.J. Saad, L.A. Velloso, and M.A. Torsoni Citrate diminishes hypothalamic acetyl-CoA carboxylase phosphorylation and modulates satiety signals and hepatic mechanisms involved in glucose homeostasis in rats Life Sci. 82 2008 1262 1271
16. S.H. Cha, and M.D. Lane Central lactate metabolism suppresses food intake via the hypothalamic AMP kinase/malonyl-CoA signaling pathway Biochem. Biophys. Res. Commun. 386 2009 212 216
17. M. Chari, C.K. Lam, P.Y. Wang, and T.K. Lam Activation of central lactate metabolism lowers glucose production in uncontrolled diabetes and diet-induced insulin resistance Diabetes 57 2008 836 840
18. X. Chen, N. Iqbal, and G. Boden The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects J. Clin. Invest. 103 1999 365 372 (Pubitemid 29069986)
19. A.D. Cherrington Banting Lecture 1997. Control of glucose uptake and release by the liver in vivo Diabetes 48 1999 1198 1214 (Pubitemid 29226371)
20. G.W. Cheung, A. Kokorovic, C.K. Lam, M. Chari, and T.K. Lam Intestinal cholecystokinin controls glucose production through a neuronal network Cell Metab. 10 2009 99 109
21. I. Chowers, S. Lavy, and L. Halpern Effect of insulin administered intracisternally on the glucose level of the blood and the cerebrospinal fluid in vagotomized dogs Exp. Neurol. 14 1966 383 389
22. C.A. Chu, S.M. Sherck, K. Igawa, D.K. Sindelar, D.W. Neal, M. Emshwiller, and A.D. Cherrington Effects of free fatty acids on hepatic glycogenolysis and gluconeogenesis in conscious dogs Am. J. Physiol. Endocrinol. Metab. 282 2002 E402 E411
23. D.J. Clegg, K. Gotoh, C. Kemp, M.D. Wortman, S.C. Benoit, L.M. Brown, D. D'Alessio, P. Tso, R.J. Seeley, and S.C. Woods Consumption of a high-fat diet induces central insulin resistance independent of adiposity Physiol. Behav. 103 2011 10 16
24. A.P. Coll, I.S. Farooqi, and S. O'Rahilly The hormonal control of food intake Cell 129 2007 251 262 (Pubitemid 46574977)
25. V.E. Cotero, and V.H. Routh Insulin blunts the response of glucose-excited neurons in the ventrolateral-ventromedial hypothalamic nucleus to decreased glucose Am. J. Physiol. Endocrinol. Metab. 296 2009 E1101 E1109
26. D.E. Cummings, and J. Overduin Gastrointestinal regulation of food intake J. Clin. Invest. 117 2007 13 23 (Pubitemid 46048445)
27. S.G. Dann, A. Selvaraj, and G. Thomas mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer Trends Mol. Med. 13 2007 252 259 (Pubitemid 46836871)
28. H. Davidowa, and A. Plagemann Inhibition by insulin of hypothalamic VMN neurons in rats overweight due to postnatal overfeeding Neuroreport 12 2001 3201 3204 (Pubitemid 33010643)
29. C.T. De Souza, E.P. Araujo, S. Bordin, R. Ashimine, R.L. Zollner, A.C. Boschero, M.J. Saad, and L.A. Velloso Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus Endocrinology 146 2005 4192 4199 (Pubitemid 41324012)
30. D.S. Edgerton, M. Lautz, M. Scott, C.A. Everett, K.M. Stettler, D.W. Neal, C.A. Chu, and A.D. Cherrington Insulin's direct effects on the liver dominate the control of hepatic glucose production J. Clin. Invest. 116 2006 521 527 (Pubitemid 43228370)
31. D.P. Figlewicz, and S.C. Benoit Insulin, leptin, and food reward: update 2008 Am. J. Physiol. Regul. Integr. Comp. Physiol. 296 2009 R9 R19
32. D.P. Figlewicz, P. Szot, M. Chavez, S.C. Woods, and R.C. Veith Intraventricular insulin increases dopamine transporter mRNA in rat VTA/substantia nigra Brain Res. 644 1994 331 334 (Pubitemid 24127991)
33. D.P. Figlewicz, S.B. Evans, J. Murphy, M. Hoen, and D.G. Baskin Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat Brain Res. 964 2003 107 115 (Pubitemid 36165075)
34. S.J. Fisher, J.C. Brüning, S. Lannon, and C.R. Kahn Insulin signaling in the central nervous system is critical for the normal sympathoadrenal response to hypoglycemia Diabetes 54 2005 1447 1451 (Pubitemid 40586676)
35. L.M. Freed, S. Wakabayashi, J.M. Bell, and S.I. Rapoport Effect of inhibition of beta-oxidation on incorporation of [U-14C]palmitate and [1-14C]arachidonate into brain lipids Brain Res. 645 1994 41 48
36. S. Gao, W. Keung, D. Serra, W. Wang, P. Carrasco, N. Casals, F.G. Hegardt, T.H. Moran, and G.D. Lopaschuk Malonyl-CoA mediates leptin hypothalamic control of feeding independent of inhibition of CPT-1a Am. J. Physiol. Regul. Integr. Comp. Physiol. 301 2011 R209 R217
37. S. Gao, G. Zhu, X. Gao, D. Wu, P. Carrasco, N. Casals, F.G. Hegardt, T.H. Moran, and G.D. Lopaschuk Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding Proc. Natl. Acad. Sci. USA 108 2011 9691 9696
38. R.W. Gelling, G.J. Morton, C.D. Morrison, K.D. Niswender, M.G. Myers Jr., C.J. Rhodes, and M.W. Schwartz Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes Cell Metab. 3 2006 67 73
39. J. German, F. Kim, G.J. Schwartz, P.J. Havel, C.J. Rhodes, M.W. Schwartz, and G.J. Morton Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a neurocircuit involving the vagus nerve Endocrinology 150 2009 4502 4511
40. J.A. Hamilton, and K. Brunaldi A model for fatty acid transport into the brain J. Mol. Neurosci. 33 2007 12 17 (Pubitemid 47574951)
41. W. He, T.K. Lam, S. Obici, and L. Rossetti Molecular disruption of hypothalamic nutrient sensing induces obesity Nat. Neurosci. 9 2006 227 233 (Pubitemid 43164546)
42. W.L. Holland, J.T. Brozinick, L.P. Wang, E.D. Hawkins, K.M. Sargent, Y. Liu, K. Narra, K.L. Hoehn, T.A. Knotts, and A. Siesky Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance Cell Metab. 5 2007 167 179
43. W.L. Holland, B.T. Bikman, L.P. Wang, G. Yuguang, K.M. Sargent, S. Bulchand, T.A. Knotts, G. Shui, D.J. Clegg, and M.R. Wenk Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice J. Clin. Invest. 121 2011 1858 1870
44. G.S. Hotamisligil Endoplasmic reticulum stress and the inflammatory basis of metabolic disease Cell 140 2010 900 917
45. Z. Hu, Y. Dai, M. Prentki, S. Chohnan, and M.D. Lane A role for hypothalamic malonyl-CoA in the control of food intake J. Biol. Chem. 280 2005 39681 39683 (Pubitemid 41779099)
46. H. Inoue, W. Ogawa, A. Asakawa, Y. Okamoto, A. Nishizawa, M. Matsumoto, K. Teshigawara, Y. Matsuki, E. Watanabe, and R. Hiramatsu Role of hepatic STAT3 in brain-insulin action on hepatic glucose production Cell Metab. 3 2006 267 275
47. P.A. Israel, C.R. Park, M.W. Schwartz, P.K. Green, A.J. Sipols, S.C. Woods, D. Porte Jr., and D.P. Figlewicz Effect of diet-induced obesity and experimental hyperinsulinemia on insulin uptake into CSF of the rat Brain Res. Bull. 30 1993 571 575 (Pubitemid 23086075)
48. K.J. Kaiyala, R.L. Prigeon, S.E. Kahn, S.C. Woods, and M.W. Schwartz Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs Diabetes 49 2000 1525 1533
49. P. Kishore, L. Boucai, K. Zhang, W. Li, S. Koppaka, S. Kehlenbrink, A. Schiwek, Y.B. Esterson, D. Mehta, and S. Bursheh Activation of K(ATP) channels suppresses glucose production in humans J. Clin. Invest. 121 2011 4916 4920
50. A. Kleinridders, D. Schenten, A.C. Könner, B.F. Belgardt, J. Mauer, T. Okamura, F.T. Wunderlich, R. Medzhitov, and J.C. Brüning MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity Cell Metab. 10 2009 249 259
51. T. Klöckener, S. Hess, B.F. Belgardt, L. Paeger, L.A. Verhagen, A. Husch, J.W. Sohn, B. Hampel, H. Dhillon, and J.M. Zigman High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons Nat. Neurosci. 14 2011 911 918
52. A. Kokorovic, G.W. Cheung, D.M. Breen, M. Chari, C.K. Lam, and T.K. Lam Duodenal mucosal protein kinase C-δ regulates glucose production in rats Gastroenterology 141 2011 1720 1727
53. A.C. Könner, R. Janoschek, L. Plum, S.D. Jordan, E. Rother, X. Ma, C. Xu, P. Enriori, B. Hampel, and G.S. Barsh Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production Cell Metab. 5 2007 438 449 (Pubitemid 46825497)
54. A.C. Könner, S. Hess, S. Tovar, A. Mesaros, C. Sánchez- Lasheras, N. Evers, L.A. Verhagen, H.S. Brönneke, A. Kleinridders, and B. Hampel Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis Cell Metab. 13 2011 720 728
55. D.Y. Kuo, S.F. Yang, S.C. Chu, S.C. Chu, C.H. Chen, and Y.S. Hsieh Amphetamine-evoked changes of oxidative stress and neuropeptide Y gene expression in hypothalamus: regulation by the protein kinase C-delta signaling Chem. Biol. Interact. 180 2009 193 201
56. T.K. Lam Neuronal regulation of homeostasis by nutrient sensing Nat. Med. 16 2010 392 395
57. T.K. Lam, H. Yoshii, C.A. Haber, E. Bogdanovic, L. Lam, I.G. Fantus, and A. Giacca Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-delta Am. J. Physiol. Endocrinol. Metab. 283 2002 E682 E691
58. T.K. Lam, R. Gutierrez-Juarez, A. Pocai, and L. Rossetti Regulation of blood glucose by hypothalamic pyruvate metabolism Science 309 2005 943 947 (Pubitemid 41099933)
59. T.K. Lam, A. Pocai, R. Gutierrez-Juarez, S. Obici, J. Bryan, L. Aguilar-Bryan, G.J. Schwartz, and L. Rossetti Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis Nat. Med. 11 2005 320 327 (Pubitemid 40460561)
60. T.K. Lam, G.J. Schwartz, and L. Rossetti Hypothalamic sensing of fatty acids Nat. Neurosci. 8 2005 579 584 (Pubitemid 40594197)
61. C.K. Lam, M. Chari, and T.K. Lam CNS regulation of glucose homeostasis Physiology (Bethesda) 24 2009 159 170
62. C.K. Lam, M. Chari, B.B. Su, G.W. Cheung, A. Kokorovic, C.S. Yang, P.Y. Wang, T.Y. Lai, and T.K. Lam Activation of N-methyl-D-aspartate (NMDA) receptors in the dorsal vagal complex lowers glucose production J. Biol. Chem. 285 2010 21913 21921
63. C.K. Lam, M. Chari, G.A. Rutter, and T.K. Lam Hypothalamic nutrient sensing activates a forebrain-hindbrain neuronal circuit to regulate glucose production in vivo Diabetes 60 2011 107 113
64. B.R. Landau, J. Wahren, V. Chandramouli, W.C. Schumann, K. Ekberg, and S.C. Kalhan Contributions of gluconeogenesis to glucose production in the fasted state J. Clin. Invest. 98 1996 378 385 (Pubitemid 26255737)
65. M.D. Lane, M. Wolfgang, S.H. Cha, and Y. Dai Regulation of food intake and energy expenditure by hypothalamic malonyl-CoA Int J Obes (Lond) 32 Suppl 4 2008 S49 S54
66. P.E. Light, C. Bladen, R.J. Winkfein, M.P. Walsh, and R.J. French Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium channels Proc. Natl. Acad. Sci. USA 97 2000 9058 9063 (Pubitemid 30626673)
67. P.J. Magistretti, O. Sorg, N. Yu, J.L. Martin, and L. Pellerin Neurotransmitters regulate energy metabolism in astrocytes: implications for the metabolic trafficking between neural cells Dev. Neurosci. 15 1993 306 312 (Pubitemid 24258164)
68. P.J. Magistretti, L. Pellerin, D.L. Rothman, and R.G. Shulman Energy on demand Science 283 1999 496 497
69. J.D. McGarry, G.P. Mannaerts, and D.W. Foster A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis J. Clin. Invest. 60 1977 265 270 (Pubitemid 8145165)
70. J.D. McGarry, S.E. Mills, C.S. Long, and D.W. Foster Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat Biochem. J. 214 1983 21 28 (Pubitemid 13070677)
71. M. Milanski, G. Degasperi, A. Coope, J. Morari, R. Denis, D.E. Cintra, D.M. Tsukumo, G. Anhe, M.E. Amaral, and H.K. Takahashi Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity J. Neurosci. 29 2009 359 370
72. J.C. Miller, J.M. Gnaedinger, and S.I. Rapoport Utilization of plasma fatty acid in rat brain: distribution of [14C]palmitate between oxidative and synthetic pathways J. Neurochem. 49 1987 1507 1514 (Pubitemid 17161373)
73. R.W. Mitchell, C.L. Edmundson, D.W. Miller, and G.M. Hatch On the mechanism of oleate transport across human brain microvessel endothelial cells J. Neurochem. 110 2009 1049 1057
74. K. Morgan, S. Obici, and L. Rossetti Hypothalamic responses to long-chain fatty acids are nutritionally regulated J. Biol. Chem. 279 2004 31139 31148 (Pubitemid 39037776)
75. G.J. Morton, D.E. Cummings, D.G. Baskin, G.S. Barsh, and M.W. Schwartz Central nervous system control of food intake and body weight Nature 443 2006 289 295 (Pubitemid 44435142)
76. S. Obici, Z. Feng, G. Karkanias, D.G. Baskin, and L. Rossetti Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats Nat. Neurosci. 5 2002 566 572 (Pubitemid 34568999)
77. S. Obici, Z. Feng, K. Morgan, D. Stein, G. Karkanias, and L. Rossetti Central administration of oleic acid inhibits glucose production and food intake Diabetes 51 2002 271 275 (Pubitemid 34764780)
78. S. Obici, B.B. Zhang, G. Karkanias, and L. Rossetti Hypothalamic insulin signaling is required for inhibition of glucose production Nat. Med. 8 2002 1376 1382 (Pubitemid 36019422)
79. S. Obici, Z. Feng, A. Arduini, R. Conti, and L. Rossetti Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production Nat. Med. 9 2003 756 761 (Pubitemid 36749226)
80. H. Ono, A. Pocai, Y. Wang, H. Sakoda, T. Asano, J.M. Backer, G.J. Schwartz, and L. Rossetti Activation of hypothalamic S6 kinase mediates diet-induced hepatic insulin resistance in rats J. Clin. Invest. 118 2008 2959 2968
81. A.W. Pardini, H.T. Nguyen, D.P. Figlewicz, D.G. Baskin, D.L. Williams, F. Kim, and M.W. Schwartz Distribution of insulin receptor substrate-2 in brain areas involved in energy homeostasis Brain Res. 1112 2006 169 178 (Pubitemid 44344616)
82. W.M. Pardridge, and W.H. Oldendorf Transport of metabolic substrates through the blood-brain barrier J. Neurochem. 28 1977 5 12 (Pubitemid 8022759)
83. L. Pellerin Food for thought: the importance of glucose and other energy substrates for sustaining brain function under varying levels of activity Diabetes Metab. 36 Suppl 3 2010 S59 S63
84. A. Pocai, T.K. Lam, R. Gutierrez-Juarez, S. Obici, G.J. Schwartz, J. Bryan, L. Aguilar-Bryan, and L. Rossetti Hypothalamic K(ATP) channels control hepatic glucose production Nature 434 2005 1026 1031 (Pubitemid 40586051)
85. A. Pocai, S. Obici, G.J. Schwartz, and L. Rossetti A brain-liver circuit regulates glucose homeostasis Cell Metab. 1 2005 53 61 (Pubitemid 43960581)
86. A. Pocai, T.K. Lam, S. Obici, R. Gutierrez-Juarez, E.D. Muse, A. Arduini, and L. Rossetti Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats J. Clin. Invest. 116 2006 1081 1091
87. K.A. Posey, D.J. Clegg, R.L. Printz, J. Byun, G.J. Morton, A. Vivekanandan-Giri, S. Pennathur, D.G. Baskin, J.W. Heinecke, and S.C. Woods Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet Am. J. Physiol. Endocrinol. Metab. 296 2009 E1003 E1012
88. N. Price, F. van der Leij, V. Jackson, C. Corstorphine, R. Thomson, A. Sorensen, and V. Zammit A novel brain-expressed protein related to carnitine palmitoyltransferase I Genomics 80 2002 433 442 (Pubitemid 35300742)
89. S. Purkayastha, H. Zhang, G. Zhang, Z. Ahmed, Y. Wang, and D. Cai Neural dysregulation of peripheral insulin action and blood pressure by brain endoplasmic reticulum stress Proc. Natl. Acad. Sci. USA 108 2011 2939 2944
90. C.J. Ramnanan, V. Saraswathi, M.S. Smith, E.P. Donahue, B. Farmer, T.D. Farmer, D. Neal, P.E. Williams, M. Lautz, and A. Mari Brain insulin action augments hepatic glycogen synthesis without suppressing glucose production or gluconeogenesis in dogs J. Clin. Invest. 121 2011 3713 3723
91. R. Ross, P.Y. Wang, M. Chari, C.K. Lam, L. Caspi, H. Ono, E.D. Muse, X. Li, R. Gutierrez-Juarez, and P.E. Light Hypothalamic protein kinase C regulates glucose production Diabetes 57 2008 2061 2065
92. T. Ruge, L. Hodson, J. Cheeseman, A.L. Dennis, B.A. Fielding, S.M. Humphreys, K.N. Frayn, and F. Karpe Fasted to fed trafficking of Fatty acids in human adipose tissue reveals a novel regulatory step for enhanced fat storage J. Clin. Endocrinol. Metab. 94 2009 1781 1788
93. V.T. Samuel, Z.X. Liu, X. Qu, B.D. Elder, S. Bilz, D. Befroy, A.J. Romanelli, and G.I. Shulman Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease J. Biol. Chem. 279 2004 32345 32353 (Pubitemid 39014687)
94. D.A. Sandoval, D. Bagnol, S.C. Woods, D.A. D'Alessio, and R.J. Seeley Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake Diabetes 57 2008 2046 2054
95. M.W. Schwartz, and D. Porte Jr. Diabetes, obesity, and the brain Science 307 2005 375 379 (Pubitemid 40139972)
96. M.W. Schwartz, A.J. Sipols, J.L. Marks, G. Sanacora, J.D. White, A. Scheurink, S.E. Kahn, D.G. Baskin, S.C. Woods, and D.P. Figlewicz Inhibition of hypothalamic neuropeptide Y gene expression by insulin Endocrinology 130 1992 3608 3616
97. H. Shi, M.V. Kokoeva, K. Inouye, I. Tzameli, H. Yin, and J.S. Flier TLR4 links innate immunity and fatty acid-induced insulin resistance J. Clin. Invest. 116 2006 3015 3025 (Pubitemid 44684486)
98. G.I. Shulman Cellular mechanisms of insulin resistance J. Clin. Invest. 106 2000 171 176 (Pubitemid 30483118)
99. D. Spanswick, M.A. Smith, S. Mirshamsi, V.H. Routh, and M.L. Ashford Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats Nat. Neurosci. 3 2000 757 758 (Pubitemid 30485698)
100. L.H. Storlien, D.E. James, K.M. Burleigh, D.J. Chisholm, and E.W. Kraegen Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats Am. J. Physiol. 251 1986 E576 E583
101. J. Wang, S. Obici, K. Morgan, N. Barzilai, Z. Feng, and L. Rossetti Overfeeding rapidly induces leptin and insulin resistance Diabetes 50 2001 2786 2791 (Pubitemid 33733130)
102. P.Y. Wang, L. Caspi, C.K. Lam, M. Chari, X. Li, P.E. Light, R. Gutierrez-Juarez, M. Ang, G.J. Schwartz, and T.K. Lam Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production Nature 452 2008 1012 1016 (Pubitemid 351589616)
103. P. Wiedmer, R. Nogueiras, F. Broglio, D. D'Alessio, and M.H. Tschöp Ghrelin, obesity and diabetes Nat. Clin. Pract. Endocrinol. Metab. 3 2007 705 712 (Pubitemid 47463707)
104. M.J. Wolfgang, and M.D. Lane Hypothalamic malonyl-CoA and CPT1c in the treatment of obesity FEBS J. 278 2011 552 558
105. M.J. Wolfgang, T. Kurama, Y. Dai, A. Suwa, M. Asaumi, S. Matsumoto, S.H. Cha, T. Shimokawa, and M.D. Lane The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis Proc. Natl. Acad. Sci. USA 103 2006 7282 7287 (Pubitemid 43727824)
106. S.C. Woods, E.C. Lotter, L.D. McKay, and D. Porte Jr. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons Nature 282 1979 503 505 (Pubitemid 10126541)
107. F.T. Wunderlich, P. Ströhle, A.C. Könner, S. Gruber, S. Tovar, H.S. Brönneke, L. Juntti-Berggren, L.S. Li, N. van Rooijen, and C. Libert Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action Cell Metab. 12 2010 237 249
108. Y. Xu, J.W. Hill, M. Fukuda, L. Gautron, J.W. Sohn, K.W. Kim, C.E. Lee, M.J. Choi, D.A. Lauzon, and H. Dhillon PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis Cell Metab. 12 2010 88 95
109. G. Yang, L. Badeanlou, J. Bielawski, A.J. Roberts, Y.A. Hannun, and F. Samad Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome Am. J. Physiol. Endocrinol. Metab. 297 2009 E211 E224
110. C.S. Yang, C.K. Lam, M. Chari, G.W. Cheung, A. Kokorovic, S. Gao, I. Leclerc, G.A. Rutter, and T.K. Lam Hypothalamic AMP-activated protein kinase regulates glucose production Diabetes 59 2010 2435 2443
111. X. Zhang, G. Zhang, H. Zhang, M. Karin, H. Bai, and D. Cai Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity Cell 135 2008 61 73