Selective insulin and leptin resistance in metabolic disorders

Cell Metabolism

Volumn 16, Issue 2, 2012, Pages 144-152

  Könner, A Christine ^a,b,c   Brüning, Jens C ^a,b,c  

^a UNIVERSITY OF COLOGNE   (Germany)

^b MAX PLANCK INSTITUTE FOR NEUROLOGICAL RESEARCH   (Germany)

^c UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; HEPATOCYTE NUCLEAR FACTOR 3BETA; INSULIN; INSULIN RECEPTOR; INSULIN RECEPTOR SUBSTRATE; LEPTIN; MAMMALIAN TARGET OF RAPAMYCIN; MELANOCORTIN 4 RECEPTOR; MICRORNA; MITOGEN ACTIVATED PROTEIN KINASE; NEUROPEPTIDE Y; PHOSPHATIDYLINOSITOL 3 KINASE; STAT3 PROTEIN; TRANSCRIPTION FACTOR FKHR;

ARCUATE NUCLEUS; ATHEROGENESIS; BODY FAT; CALORIC INTAKE; CENTRAL NERVOUS SYSTEM; ENERGY EXPENDITURE; FOOD INTAKE; GLUCONEOGENESIS; GLUCOSE METABOLISM; GLUCOSE TOLERANCE; GLYCOGEN SYNTHESIS; HOMEOSTASIS; HORMONE RESISTANCE; HUMAN; INSULIN RESISTANCE; LIPID METABOLISM; LIPOGENESIS; METABOLIC DISORDER; NONHUMAN; OBESITY; PARAVENTRICULAR THALAMIC NUCLEUS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; ZONA INCERTA;

CENTRAL NERVOUS SYSTEM; HUMANS; INSULIN RESISTANCE; LEPTIN; METABOLIC DISEASES; OBESITY; SIGNAL TRANSDUCTION;

EID: 84864710223     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2012.07.004     Document Type: Review

References (107)

1. M. Aizawa-Abe, Y. Ogawa, H. Masuzaki, K. Ebihara, N. Satoh, H. Iwai, N. Matsuoka, T. Hayashi, K. Hosoda, and G. Inoue Pathophysiological role of leptin in obesity-related hypertension J. Clin. Invest. 105 2000 1243 1252 (Pubitemid 30266077)
2. K. Almind, G. Inoue, O. Pedersen, and C.R. Kahn A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling. Evidence from transfection studies J. Clin. Invest. 97 1996 2569 2575
3. Y. Aponte, D. Atasoy, and S.M. Sternson AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training Nat. Neurosci. 14 2011 351 355
4. S.H. Bates, W.H. Stearns, T.A. Dundon, M. Schubert, A.W. Tso, Y. Wang, A.S. Banks, H.J. Lavery, A.K. Haq, and E. Maratos-Flier STAT3 signalling is required for leptin regulation of energy balance but not reproduction Nature 421 2003 856 859 (Pubitemid 36254146)
5. J. Baumgartl, S. Baudler, M. Scherner, V. Babaev, L. Makowski, J. Suttles, M. McDuffie, K. Tobe, T. Kadowaki, and S. Fazio Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis Cell Metab. 3 2006 247 256
6. B.F. Belgardt, and J.C. Bruning CNS leptin and insulin action in the control of energy homeostasis Ann. N Y Acad. Sci. 1212 2010 97 113
7. B.F. Belgardt, A. Husch, E. Rother, M.B. Ernst, F.T. Wunderlich, B. Hampel, T. Klockener, D. Alessi, P. Kloppenburg, and J.C. Bruning PDK1 deficiency in POMC-expressing cells reveals FOXO1-dependent and -independent pathways in control of energy homeostasis and stress response Cell Metab. 7 2008 291 301 (Pubitemid 351467391)
8. B.F. Belgardt, J. Mauer, and J.C. Bruning Novel roles for JNK1 in metabolism Aging (Albany NY) 2 2010 621 626
9. B.F. Belgardt, J. Mauer, F.T. Wunderlich, M.B. Ernst, M. Pal, G. Spohn, H.S. Bronneke, S. Brodesser, B. Hampel, A.C. Schauss, and J.C. Bruning Hypothalamic and pituitary c-Jun N-terminal kinase 1 signaling coordinately regulates glucose metabolism Proc. Natl. Acad. Sci. USA 107 2010 6028 6033
10. S.B. Biddinger, and C.R. Kahn From mice to men: insights into the insulin resistance syndromes Annu. Rev. Physiol. 68 2006 123 158
11. S.B. Biddinger, A. Hernandez-Ono, C. Rask-Madsen, J.T. Haas, J.O. Aleman, R. Suzuki, E.F. Scapa, C. Agarwal, M.C. Carey, and G. Stephanopoulos Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis Cell Metab. 7 2008 125 134 (Pubitemid 351168555)
12. M.S. Brown, and J.L. Goldstein Selective versus total insulin resistance: a pathogenic paradox Cell Metab. 7 2008 95 96 (Pubitemid 351168559)
13. J.C. Bruning, J. Winnay, S. Bonner-Weir, S.I. Taylor, D. Accili, and C.R. Kahn Development of a novel polygenic model of NIDDM in mice heterozygous for IR and IRS-1 null alleles Cell 88 1997 561 572 (Pubitemid 27154421)
14. J.C. Bruning, D. Gautam, D.J. Burks, J. Gillette, M. Schubert, P.C. Orban, R. Klein, W. Krone, D. Muller-Wieland, and C.R. Kahn Role of brain insulin receptor in control of body weight and reproduction Science 289 2000 2122 2125
15. J.B. Carvalheira, E.B. Ribeiro, E.P. Araujo, R.B. Guimaraes, M.M. Telles, M. Torsoni, J.A. Gontijo, L.A. Velloso, and M.J. Saad Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats Diabetologia 46 2003 1629 1640 (Pubitemid 38005325)
16. 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
17. P. Cohen, C. Zhao, X. Cai, J.M. Montez, S.C. Rohani, P. Feinstein, P. Mombaerts, and J.M. Friedman Selective deletion of leptin receptor in neurons leads to obesity J. Clin. Invest. 108 2001 1113 1121 (Pubitemid 32995369)
18. R.D. Cone Studies on the physiological functions of the melanocortin system Endocr. Rev. 27 2006 736 749 (Pubitemid 44936057)
19. M.L. Correia, and K. Rahmouni Role of leptin in the cardiovascular and endocrine complications of metabolic syndrome Diabetes Obes. Metab. 8 2006 603 610 (Pubitemid 44515557)
20. M.L. Correia, W.G. Haynes, K. Rahmouni, D.A. Morgan, W.I. Sivitz, and A.L. Mark The concept of selective leptin resistance: evidence from agouti yellow obese mice Diabetes 51 2002 439 442 (Pubitemid 34764800)
21. M.A. Cowley, J.L. Smart, M. Rubinstein, M.G. Cerdan, S. Diano, T.L. Horvath, R.D. Cone, and M.J. Low Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus Nature 411 2001 480 484 (Pubitemid 32494394)
22. K. Cusi, K. Maezono, A. Osman, M. Pendergrass, M.E. Patti, T. Pratipanawatr, R.A. DeFronzo, C.R. Kahn, and L.J. Mandarino Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle J. Clin. Invest. 105 2000 311 320 (Pubitemid 30094451)
23. 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)
24. A. El Ouaamari, N. Baroukh, G.A. Martens, P. Lebrun, D. Pipeleers, and E. van Obberghen miR-375 targets 3′-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells Diabetes 57 2008 2708 2717
25. P.J. Enriori, P. Sinnayah, S.E. Simonds, C. Garcia Rudaz, and M.A. Cowley Leptin action in the dorsomedial hypothalamus increases sympathetic tone to brown adipose tissue in spite of systemic leptin resistance J. Neurosci. 31 2011 12189 12197
26. I.S. Farooqi, and S. O'Rahilly Leptin: a pivotal regulator of human energy homeostasis Am. J. Clin. Nutr. 89 2009 980S 984S
27. P. Ferre, and F. Foufelle SREBP-1c transcription factor and lipid homeostasis: clinical perspective Horm. Res. 68 2007 72 82 (Pubitemid 47026704)
28. R.C. Frederich, A. Hamann, S. Anderson, B. Lollmann, B.B. Lowell, and J.S. Flier Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action Nat. Med. 1 1995 1311 1314
29. J.M. Friedman Leptin at 14 y of age: an ongoing story Am. J. Clin. Nutr. 89 2009 973S 979S
30. J.M. Friedman Obesity: causes and control of excess body fat Nature 459 2009 340 342
31. Q. Gao, and T.L. Horvath Neurobiology of feeding and energy expenditure Annu. Rev. Neurosci. 30 2007 367 398 (Pubitemid 47218761)
32. Q. Gao, M.J. Wolfgang, S. Neschen, K. Morino, T.L. Horvath, G.I. Shulman, and X.Y. Fu Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation Proc. Natl. Acad. Sci. USA 101 2004 4661 4666 (Pubitemid 38437467)
33. L. Gautron, and J.K. Elmquist Sixteen years and counting: an update on leptin in energy balance J. Clin. Invest. 121 2011 2087 2093
34. 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
35. L.J. Goodyear, F. Giorgino, L.A. Sherman, J. Carey, R.J. Smith, and G.L. Dohm Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects J. Clin. Invest. 95 1995 2195 2204
36. E. Gropp, M. Shanabrough, E. Borok, A.W. Xu, R. Janoschek, T. Buch, L. Plum, N. Balthasar, B. Hampel, and A. Waisman Agouti-related peptide-expressing neurons are mandatory for feeding Nat. Neurosci. 8 2005 1289 1291 (Pubitemid 41630413)
37. S. Han, C.P. Liang, T. DeVries-Seimon, M. Ranalletta, C.L. Welch, K. Collins-Fletcher, D. Accili, I. Tabas, and A.R. Tall Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and necrotic core formation in advanced atherosclerotic lesions Cell Metab. 3 2006 257 266
38. J.W. Hill, K.W. Williams, C. Ye, J. Luo, N. Balthasar, R. Coppari, M.A. Cowley, L.C. Cantley, B.B. Lowell, and J.K. Elmquist Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in mice J. Clin. Invest. 118 2008 1796 1805 (Pubitemid 351632382)
39. G.S. Hotamisligil Inflammation and metabolic disorders Nature 444 2006 860 867 (Pubitemid 46024993)
40. Z.Y. Jiang, Y.W. Lin, A. Clemont, E.P. Feener, K.D. Hein, M. Igarashi, T. Yamauchi, M.F. White, and G.L. King Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats J. Clin. Invest. 104 1999 447 457 (Pubitemid 29534329)
41. S.D. Jordan, M. Kruger, D.M. Willmes, N. Redemann, F.T. Wunderlich, H.S. Bronneke, C. Merkwirth, H. Kashkar, V.M. Olkkonen, and T. Bottger Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism Nat. Cell Biol. 13 2011 434 446
42. C.R. Kahn Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes Diabetes 43 1994 1066 1084 (Pubitemid 24230714)
43. P. Kievit, J.K. Howard, M.K. Badman, N. Balthasar, R. Coppari, H. Mori, C.E. Lee, J.K. Elmquist, A. Yoshimura, and J.S. Flier Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells Cell Metab. 4 2006 123 132 (Pubitemid 44138722)
44. Y.B. Kim, S.E. Nikoulina, T.P. Ciaraldi, R.R. Henry, and B.B. Kahn Normal insulin-dependent activation of Akt/protein kinase B, with diminished activation of phosphoinositide 3-kinase, in muscle in type 2 diabetes J. Clin. Invest. 104 1999 733 741 (Pubitemid 29536358)
45. A. Kleinridders, D. Schenten, A.C. Konner, B.F. Belgardt, J. Mauer, T. Okamura, F.T. Wunderlich, R. Medzhitov, and J.C. Bruning 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
46. T. Klockener, 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
47. L. Koch, F.T. Wunderlich, J. Seibler, A.C. Konner, B. Hampel, S. Irlenbusch, G. Brabant, C.R. Kahn, F. Schwenk, and J.C. Bruning Central insulin action regulates peripheral glucose and fat metabolism in mice J. Clin. Invest. 118 2008 2132 2147 (Pubitemid 351872332)
48. A.C. Konner, and J.C. Bruning Toll-like receptors: linking inflammation to metabolism Trends Endocrinol. Metab. 22 2011 16 23
49. A.C. Konner, 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)
50. A.C. Konner, T. Klockener, and J.C. Bruning Control of energy homeostasis by insulin and leptin: targeting the arcuate nucleus and beyond Physiol. Behav. 97 2009 632 638
51. A.C. Konner, S. Hess, S. Tovar, A. Mesaros, C. Sanchez-Lasheras, N. Evers, L.A. Verhagen, H.S. Bronneke, A. Kleinridders, and B. Hampel Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis Cell Metab. 13 2011 720 728
52. M.J. Krashes, S. Koda, C. Ye, S.C. Rogan, A.C. Adams, D.S. Cusher, E. Maratos-Flier, B.L. Roth, and B.B. Lowell Rapid, reversible activation of AgRP neurons drives feeding behavior in mice J. Clin. Invest. 121 2011 1424 1428
53. J. Krutzfeldt, and M. Stoffel MicroRNAs: a new class of regulatory genes affecting metabolism Cell Metab. 4 2006 9 12 (Pubitemid 43942256)
54. M. Laplante, and D.M. Sabatini mTORC1 activates SREBP-1c and uncouples lipogenesis from gluconeogenesis Proc. Natl. Acad. Sci. USA 107 2010 3281 3282
55. B.E. Levin, and R.S. Sherwin Peripheral glucose homeostasis: does brain insulin matter? J. Clin. Invest. 121 2011 3392 3395
56. S. Li, M.S. Brown, and J.L. Goldstein Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis Proc. Natl. Acad. Sci. USA 107 2010 3441 3446
57. C.P. Liang, S. Han, T. Senokuchi, and A.R. Tall The macrophage at the crossroads of insulin resistance and atherosclerosis Circ. Res. 100 2007 1546 1555 (Pubitemid 46897258)
58. C.N. Lumeng, and A.R. Saltiel Inflammatory links between obesity and metabolic disease J. Clin. Invest. 121 2011 2111 2117
59. S. Luquet, F.A. Perez, T.S. Hnasko, and R.D. Palmiter NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates Science 310 2005 683 685 (Pubitemid 41528162)
60. M. Maffei, J. Halaas, E. Ravussin, R.E. Pratley, G.H. Lee, Y. Zhang, H. Fei, S. Kim, R. Lallone, and S. Ranganathan Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects Nat. Med. 1 1995 1155 1161
61. A.L. Mark, R.A. Shaffer, M.L. Correia, D.A. Morgan, C.D. Sigmund, and W.G. Haynes Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice J. Hypertens. 17 1999 1949 1953 (Pubitemid 30345336)
62. A.L. Mark, M.L. Correia, K. Rahmouni, and W.G. Haynes Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications J. Hypertens. 20 2002 1245 1250 (Pubitemid 34925659)
63. J. Mauer, B. Chaurasia, L. Plum, T. Quast, B. Hampel, M. Bluher, W. Kolanus, C.R. Kahn, and J.C. Bruning Myeloid cell-restricted insulin receptor deficiency protects against obesity-induced inflammation and systemic insulin resistance PLoS Genet. 6 2010 e1000938 10.1371/journal.pgen.1000938
64. C.M. Mayer, and D.D. Belsham Central insulin signaling is attenuated by long-term insulin exposure via insulin receptor substrate-1 serine phosphorylation, proteasomal degradation, and lysosomal insulin receptor degradation Endocrinology 151 2010 75 84
65. C.M. Mayer, and D.D. Belsham Palmitate attenuates insulin signaling and induces endoplasmic reticulum stress and apoptosis in hypothalamic neurons: rescue of resistance and apoptosis through adenosine 5′ monophosphate-activated protein kinase activation Endocrinology 151 2010 576 585
66. M.C. Mendoza, E.E. Er, and J. Blenis The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation Trends Biochem. Sci. 36 2011 320 328
67. A.H. Mokdad, E.S. Ford, B.A. Bowman, W.H. Dietz, F. Vinicor, V.S. Bales, and J.S. Marks Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001 JAMA 289 2003 76 79 (Pubitemid 36026281)
68. H. Mori, R. Hanada, T. Hanada, D. Aki, R. Mashima, H. Nishinakamura, T. Torisu, K.R. Chien, H. Yasukawa, and A. Yoshimura Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity Nat. Med. 10 2004 739 743 (Pubitemid 38937640)
69. 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)
70. A. Mullier, S.G. Bouret, V. Prevot, and B. Dehouck Differential distribution of tight junction proteins suggests a role for tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain J. Comp. Neurol. 518 2010 943 962
71. H. Munzberg, J.S. Flier, and C. Bjorbaek Region-specific leptin resistance within the hypothalamus of diet-induced obese mice Endocrinology 145 2004 4880 4889 (Pubitemid 39551104)
72. D.M. Muoio, and C.B. Newgard Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes Nat. Rev. Mol. Cell Biol. 9 2008 193 205 (Pubitemid 351301824)
73. M.G. Myers Jr., R.L. Leibel, R.J. Seeley, and M.W. Schwartz Obesity and leptin resistance: distinguishing cause from effect Trends Endocrinol. Metab. 21 2010 643 651
74. K.D. Niswender, and M.W. Schwartz Insulin and leptin revisited: adiposity signals with overlapping physiological and intracellular signaling capabilities Front. Neuroendocrinol. 24 2003 1 10 (Pubitemid 36263453)
75. K.D. Niswender, G.J. Morton, W.H. Stearns, C.J. Rhodes, M.G. Myers Jr., and M.W. Schwartz Intracellular signalling. Key enzyme in leptin-induced anorexia Nature 413 2001 794 795 (Pubitemid 33026839)
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, 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)
78. G. Perseghin, E. Regalia, A. Battezzati, S. Vergani, A. Pulvirenti, I. Terruzzi, D. Baratti, F. Bozzetti, V. Mazzaferro, and L. Luzi Regulation of glucose homeostasis in humans with denervated livers J. Clin. Invest. 100 1997 931 941 (Pubitemid 27371712)
79. L. Plum, B.F. Belgardt, and J.C. Bruning Central insulin action in energy and glucose homeostasis J. Clin. Invest. 116 2006 1761 1766 (Pubitemid 44033295)
80. L. Plum, X. Ma, B. Hampel, N. Balthasar, R. Coppari, H. Munzberg, M. Shanabrough, D. Burdakov, E. Rother, and R. Janoschek Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity J. Clin. Invest. 116 2006 1886 1901 (Pubitemid 44033313)
81. L. Plum, E. Rother, H. Munzberg, F.T. Wunderlich, D.A. Morgan, B. Hampel, M. Shanabrough, R. Janoschek, A.C. Konner, and J. Alber Enhanced leptin-stimulated Pi3k activation in the CNS promotes white adipose tissue transdifferentiation Cell Metab. 6 2007 431 445 (Pubitemid 350163053)
82. L. Plum, H.V. Lin, R. Dutia, J. Tanaka, K.S. Aizawa, M. Matsumoto, A.J. Kim, N.X. Cawley, J.H. Paik, and Y.P. Loh The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake Nat. Med. 15 2009 1195 1201
83. 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
84. K. Rahmouni, W.G. Haynes, D.A. Morgan, and A.L. Mark Selective resistance to central neural administration of leptin in agouti obese mice Hypertension 39 2002 486 490 (Pubitemid 34165170)
85. K. Rahmouni, D.A. Morgan, G.M. Morgan, A.L. Mark, and W.G. Haynes Role of selective leptin resistance in diet-induced obesity hypertension Diabetes 54 2005 2012 2018 (Pubitemid 40911263)
86. 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
87. C. Rask-Madsen, and G.L. King Mechanisms of disease: endothelial dysfunction in insulin resistance and diabetes Nat. Clin. Pract. Endocrinol. Metab. 3 2007 46 56 (Pubitemid 46006612)
88. C. Rask-Madsen, Q. Li, B. Freund, D. Feather, R. Abramov, I.H. Wu, K. Chen, J. Yamamoto-Hiraoka, J. Goldenbogen, and K.B. Sotiropoulos Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein E null mice Cell Metab. 11 2010 379 389
89. G.M. Reaven Why Syndrome X? From Harold Himsworth to the insulin resistance syndrome Cell Metab. 1 2005 9 14 (Pubitemid 43960585)
90. G. Sabio, J. Cavanagh-Kyros, T. Barrett, D.Y. Jung, H.J. Ko, H. Ong, C. Morel, A. Mora, J. Reilly, J.K. Kim, and R.J. Davis Role of the hypothalamic-pituitary-thyroid axis in metabolic regulation by JNK1 Genes Dev. 24 2010 256 264
91. T. Scherer, J. O'Hare, K. Diggs-Andrews, M. Schweiger, B. Cheng, C. Lindtner, E. Zielinski, P. Vempati, K. Su, and S. Dighe Brain insulin controls adipose tissue lipolysis and lipogenesis Cell Metab. 13 2011 183 194
92. M. Schubert, D. Gautam, D. Surjo, K. Ueki, S. Baudler, D. Schubert, T. Kondo, J. Alber, N. Galldiks, and E. Kustermann Role for neuronal insulin resistance in neurodegenerative diseases Proc. Natl. Acad. Sci. USA 101 2004 3100 3105 (Pubitemid 38327741)
93. R.K. Semple, D.B. Savage, E.K. Cochran, P. Gorden, and S. O'Rahilly Genetic syndromes of severe insulin resistance Endocr. Rev. 32 2011 498 514
94. T. Senokuchi, C.P. Liang, T.A. Seimon, S. Han, M. Matsumoto, A.S. Banks, J.H. Paik, R.A. DePinho, D. Accili, I. Tabas, and A.R. Tall Forkhead transcription factors (FoxOs) promote apoptosis of insulin-resistant macrophages during cholesterol-induced endoplasmic reticulum stress Diabetes 57 2008 2967 2976
95. E.W. Shek, M.W. Brands, and J.E. Hall Chronic leptin infusion increases arterial pressure Hypertension 31 1998 409 414
96. S.M. Sternson, G.M. Shepherd, and J.M. Friedman Topographic mapping of VMH-> arcuate nucleus microcircuits and their reorganization by fasting Nat. Neurosci. 8 2005 1356 1363 (Pubitemid 41630424)
97. C.M. Taniguchi, B. Emanuelli, and C.R. Kahn Critical nodes in signalling pathways: insights into insulin action Nat. Rev. Mol. Cell Biol. 7 2006 85 96 (Pubitemid 43278292)
98. J.F. Tanti, and J. Jager Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation Curr. Opin. Pharmacol. 9 2009 753 762
99. J.P. Thaler, S.J. Choi, M.W. Schwartz, and B.E. Wisse Hypothalamic inflammation and energy homeostasis: resolving the paradox Front. Neuroendocrinol. 31 2010 79 84
100. Q. Tong, C.P. Ye, J.E. Jones, J.K. Elmquist, and B.B. Lowell Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance Nat. Neurosci. 11 2008 998 1000
101. M. Trajkovski, J. Hausser, J. Soutschek, B. Bhat, A. Akin, M. Zavolan, M.H. Heim, and M. Stoffel MicroRNAs 103 and 107 regulate insulin sensitivity Nature 474 2011 649 653
102. C. Vaisse, J.L. Halaas, C.M. Horvath, J.E. Darnell Jr., M. Stoffel, and J.M. Friedman Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice Nat. Genet. 14 1996 95 97 (Pubitemid 26301554)
103. M.F. White Insulin signaling in health and disease Science 302 2003 1710 1711 (Pubitemid 37505726)
104. WHO (2006). Obesity and overweight. Fact sheet number 311. http://www.who.int/mediacentre/factsheets/fs311/en/index.html.
105. C. Wolfrum, E. Asilmaz, E. Luca, J.M. Friedman, and M. Stoffel Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes Nature 432 2004 1027 1032 (Pubitemid 40052233)
106. Y. Xu, J.K. Elmquist, and M. Fukuda Central nervous control of energy and glucose balance: focus on the central melanocortin system Ann. N Y Acad. Sci. 1243 2011 1 14
107. Y. Zhang, R. Proenca, M. Maffei, M. Barone, L. Leopold, and J.M. Friedman Positional cloning of the mouse obese gene and its human homologue Nature 372 1994 425 432 (Pubitemid 24365442)