Balancing Mitochondrial redox signaling: A key point in metabolic regulation

Antioxidants and Redox Signaling

Volumn 14, Issue 3, 2011, Pages 519-530

  Leloup, Corinne ^a   Casteilla, Louis ^b,c   Carrière, Audrey ^b,c   Galinier, Anne ^b,c   Benani, Alexandre ^a   Carneiro, Lionel ^a   Pénicaud, Luc ^a  

^a CENTRE DES SCIENCES DU GOÛT ET DE L ALIMENTATION   (France)

^b UNIVERSITÉ DE TOULOUSE   (France)

^c CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

REACTIVE OXYGEN METABOLITE;

ADIPOGENESIS; ADIPOSE TISSUE; ENERGY METABOLISM; HYPOTHALAMUS; METABOLIC REGULATION; MITOCHONDRION; OXIDATION REDUCTION REACTION; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; REVIEW;

ADIPOGENESIS; ANIMALS; BLOOD GLUCOSE; HUMANS; HYPOTHALAMUS; INSULIN-SECRETING CELLS; ION CHANNELS; MITOCHONDRIA; MITOCHONDRIAL PROTEINS; NEURONS; OXIDATION-REDUCTION; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION;

EID: 78650874299     PISSN: 15230864     EISSN: None     Source Type: Journal    
DOI: 10.1089/ars.2010.3424     Document Type: Review

References (113)

1. Abizaid A and Horvath TL. Brain circuits regulating energy homeostasis. Regul Pept 149: 3-10, 2008.
2. Adam-Vizi V. Production of reactive oxygen species in brain mitochondria: contribution by electron transport chain and non-electron transport chain sources. Antioxid Redox Signal 7: 1140-1149, 2005.
3. Ainscow EK, Mirshamsi S, Tang T, Ashford ML, and Rutter GA. Dynamic imaging of free cytosolic ATP concentration during fuel sensing by rat hypothalamic neurones: evidence for ATP-independent control of ATP-sensitive K(\+) channels. J Physiol 544: 429-445, 2002.
4. Alquier T, Leloup C, Atef N, Fioramonti X, Lorsignol A, and Pénicaud L. Cerebral insulin increases brain response to glucose. J Neuroendocrinol 15: 75-79, 2003.
5. Andrews ZB, Liu ZW, Walllingford N, Erion DM, Borok E, Friedman JM, Tschöp MH, Shanabrough M, Cline G, Shulman GI, Coppola A, Gao XB, Horvath TL, and Diano S. UCP2 mediates ghrelin's action on NPY=AgRP neurons by lowering free radicals. Nature 454: 846-851, 2008.
6. Arkblad EL, Tuck S, Pestov NB, Dmitriev RI, Kostina MB, Stenvall J, Tranberg M, and Rydström J. A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxida-tive stress. Free Radic Biol Med 38: 1518-1525, 2005.
7. Avshalumov MV and Rice ME. Activation of ATP-sensitive K\+ (K(ATP)) channels by H2O2 underlies glutamate-dependent inhibition of striatal dopamine release. Proc Natl Acad Sci USA 100: 11729-11734, 2003.
8. Azzu V and Brand MD. The on-off switches of the mito-chondrial uncoupling proteins. Trends Biochem Sci 35: 298- 307, 2010.
9. Bao L, Avshalumov MV, Patel JC, Lee CR, Miller EW, Chang CJ, and Rice ME. Mitochondria are the source of hydrogen peroxide for dynamic brain-cell signaling. J Neurosci 29: 9002-9010, 2009.
10. Barja G. Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity, and relation to aging and longevity. J Bioenerg Biomembr 31: 347-366, 1999.
11. Benani A, Troy S, Carmona MC, Fioramonti X, Lorsignol A, Leloup C, Casteilla L, and Pénicaud L. Role for mitochon-drial reactive oxygen species in brain lipid sensing: redox regulation of food intake. Diabetes 56: 152-160, 2007.
12. Berniakovich I, Trinei M, Stendardo M, Migliaccio E, Minucci S, Bernardi P, Pelicci PG, and Giorgio M. p66Shc-generated oxidative signal promotes fat accumulation. J Biol Chem 283: 34283-34293, 2008.
13. Bienert GP, Møller AL, Kristiansen KA, Schulz A, Møller IM, Schjoerring JK, and Jahn TP. Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J Biol Chem 282: 1183-1192, 2007.
14. Bindokas VP, Kuznetsov A, Sreenan S, Polonsky KS, Roe MW, and Philipson LH. Visualizing superoxide production in normal and diabetic rat islets of Langerhans. J Biol Chem 278: 9796-9801, 2003.
15. Bouillaud F. UCP2, not a physiologically relevant un-coupler but a glucose sparing switch impacting ROS production and glucose sensing. Biochim Biophys Acta 1787: 377-383, 2009.
16. Brand MD. The sites and topology of mitochondrial su-peroxide production. Exp Gerontol 45: 466-472, 2010.
17. Bray GA. Afferent signals regulating food intake. Proc Nutr Soc 59: 373-384, 2000.
18. Cadenas E, Boveris A, Ragan CI, and Stoppani AO. Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria. Arch Biochem Bio-phys 180: 248-257, 1977.
19. Carrière A, Carmona MC, Fernandez Y, Rigoulet M, Wenger RH, Pénicaud L, and Casteilla L. Mitochondrial reactive oxygen species control the transcription factor CHOP-10=GADD153 and adipocyte differentiation: a mechanism for hypoxia-dependent effect. J Biol Chem 279: 40462-40469, 2004.
20. Carrière A, Ebrahimian TG, Dehez S, Augé N, Joffre C, André M, Arnal S, Duriez M, Barreau C, Arnaud E, Fernandez Y, Planat-Benard V, Lévy B, Pénicaud L, Silvestre JS, and Casteilla L. Preconditioning by mitochondrial reactive oxygen species improves the proangiogenic potential of adipose-derived cells-based therapy. Arterioscler Thromb Vasc Biol 29: 1093-1099, 2009.
21. Carrière A, Fernandez Y, Rigoulet M, Pénicaud L, and Casteilla L. Inhibition of preadipocyte proliferation by mi-tochondrial reactive oxygen species. FEBS Lett 550: 163-167, 2003.
22. Casteilla L, Rigoulet M, and Pénicaud L. Mitochondrial ROS metabolism: modulation by uncoupling proteins. IUBMB Life 52: 181-188, 2001.
23. Chan CB and Harper ME. Uncoupling proteins: role in insulin resistance and insulin insufficiency. Curr Diabetes Rev 2: 271-283, 2006.
24. Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, and Schumacker PT. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci USA, 95: 11715-11720, 1998.
25. Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, and Lesnefsky EJ. Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem 278: 36027-36031, 2003.
26. Chevillotte E, Giralt M, Miroux B, Ricquier D, and Villarroya. Uncoupling protein-2 controls adiponectin gene expression in adipose tissue through the modulation of reactive oxygen species production. Diabetes 56: 1042-1050, 2007.
27. Colombani AL, Carneiro L, Benani A, Galinier A, Jaillard T, Duparc T, Offer G, Lorsignol A, Magnan C, Casteilla L, Pénicaud L, and Leloup C. Enhanced hypothalamic glucose sensing in obesity: alteration of redox signaling. Diabetes 58: 2189-2197, 2009.
28. Coppola A, Liu ZW, Andrews ZB, Paradis E, Roy MC, Friedman JM, Ricquier D, Richard D, Horvath TL, Gao XB, and Diano S. A central thermogenic-like mechanism in feeding regulation: an interplay between arcuate nucleus T3 and UCP2. Cell Metab 5: 21-33, 2007.
29. Curtis JM, Grimsrud PA, Wright WS, Xu X, Foncea RE, Graham DW, Brestoff JR, Wiczer BM, Ilkayeva O, Cian-flone K, Muoio DE, Arriaga EA, and Bernlohr DA. Down regulation of adipose glutathione S-transferase leads to increased protein carbonylation, oxidative stress and mi-tochondrial dysfunction. Diabetes 59: 1132-1142, 2010.
30. De Pauw A, Tejerina S, Raes M, Keijer J, and Arnould T. Mitochondrial (dys)function in adipocyte (de)differentia-tion and systemic metabolic alterations Am J Pathol 175: 927-939, 2009.
31. Deierborg T, Wieloch T, Diano S, Warden CH, Horvath TL, and Mattiasson G. Overexpression of UCP2 protects tha-lamic neurons following global ischemia in the mouse. J Cereb Blood Flow Metab 28: 1186-1195, 2008.
32. 0-deoxythymidine (AZT)-treated rats: an early stage in lipodystrophy? Biochem Pharmacol 70: 90-101, 2005.
33. Dröge W. Free radicals in the physiological control of cell function. Physiol Rev 82: 47-95, 2002.
34. Echtay KS, Murphy MP, Smith RA, Talbot DA, and Brand MD. Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antiox-idants. J Biol Chem 277: 47129-47135, 2002.
35. Echtay KS. Mitochondrial uncoupling proteins-what is their physiological role? Free Radic Biol Med 43: 1351-1371, 2007.
36. Fioramonti X, Lorsignol A, Taupignon A, and Pénicaud L. A new ATP-sensitive K\+ channel-independent mechanism is involved in glucose-excited neurons of mouse arcuate nucleus. Diabetes 3: 2767-2775, 2004.
37. Forman HJ, Fukuto JM, and Torres M. Redox signaling: thiol chemistry defines which reactive oxygen and nitrogen species can act as second messengers. Am J Physiol Cell Physiol 287: C246-C256, 2004.
38. Freeman H, Shimomura K, Horner E, Cox RD, and Ash-croft FM. Nicotinamide nucleotide transhydrogenase: a key role in insulin secretion. Cell Metab 3: 35-45, 2006.
39. Galinier A, Carrière A, Fernandez Y, Carpéné C, André M, Caspar-Bauguil S, Thouvenot JP, Périquet B, Pénicaud L, and Casteilla L. Adipose tissue proadipogenic redox changes in obesity. J Biol Chem 281: 12682-12687, 2006.
40. Gao CL, Zhu C, Zhao YP, Chen XH, Ji CB, Zhang CM, Zhu JG, Xia ZK, Tong ML, and Guo XR. Mitochondrial dysfunction is induced by high levels of glucose and free fatty acids in 3T3-L1 adipocytes. Mol Cell Endocrinol 320: 25-33, 2010.
41. Gertz M and Steegborn C. The lifespan-regulator p66Shc in mitochondria: redox enzyme or redox sensor? Antioxid Redox Signal 13: 1417-1428, 2010.
42. Gier B, Krippeit-Drews P, Sheiko T, Aguilar-Bryan L, Bryan J, Düfer M, and Drews G. Suppression of KATP channel activity protects murine pancreatic beta cells against oxi-dative stress. J Clin Invest 119: 3246-3256, 2009.
43. Gimble JM, Katz AJ, and Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res 100: 1249-1260, 2007.
44. Goldstein BJ, Mahadev K, Wu X, Zhu L, and Motoshima H. Role of insulin-induced reactive oxygen species in the insulin signaling pathway. Antioxid Redox Signal 7: 1021-1031, 2005.
45. Görlach A, Klappa P, and Kietzmann T. The endoplasmic reticulum: folding, calcium homeostasis, signaling, and redox control. Antioxid Redox Signal 8: 1391-1420, 2006.
46. Hamanaka RB and Chandel NS. Mitochondrial reactive oxygen species regulate hypoxic signaling. Curr Opin Cell Bio 21: 894-899, 2009.
47. Han D, Williams E, and Cadenas E. Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space. Biochem J 353: 411-416, 2001.
48. 2\+ -permeable channel activated by changes in redox status confers susceptibility to cell death. Moll Cell 9: 163-173, 2002.
49. Hawley SA, Ross FA, Chevtzoff C, Green KA, Evans A, Fogarty S, Towler MC, Brown LJ, Ogunbayo OA, Evans AM, and Hardie DG. Use of cells expressing gamma sub-unit variants to identify diverse mechanisms of AMPK activation. Cell Metab 11: 554-565, 2010.
50. Henquin JC. Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49: 1751-1760, 2000.
51. Hoehn KL, Salmon AB, Hohnen-Behrens C, Turner N, Hoy AJ, Maghzal GJ, Stocker R, Van Remmen H, Kraegen EW, Cooney GJ, Richardson AR, and James DE. Insulin resistance is a cellular antioxidant defense mechanism. Proc Natl Acad Sci USA 106: 17787-17792, 2009.
52. Hoek JB and Rydström J. Physiological roles of nicotin-amide nucleotide transhydrogenase. Biochem J 254: 1-10, 1988.
53. Horvath TL, Andrews ZB, and Diano S. Fuel utilization by hypothalamic neurons: roles for ROS. Trends Endocrinol Metab 20: 78-87, 2009.
54. Hou N, Torii S, Saito N, Hosaka M, and Takeushi T. Reactive oxygen species-mediated pancreatic b-cell death is regulated by interactions between stress-activated protein kinases, p38 and c-Jun N-terminal kinase, and mitogen-activated protein kinase phosphatases. Endocrinology 149: 1654-1665, 2009.
55. Jacobson DA and Philipson LH. TRP channels of the pancreatic beta cell. Handb Exp Pharmacol 179: 409-424, 2007.
56. Janssen-Heininger YM, Mossman BT, Heintz NH, Forman HJ, Kalyanaraman B, Finkel T, Stamler JS, Rhee SG, and van der Vliet A. Redox-based regulation of signal trans-duction: principles, pitfalls, and promises. Free Radic Biol Med 45: 1-17, 2008.
57. Kolisek M, Beck A, Fleig A, and Penner R. Cyclic ADP-ribose and hydrogen peroxide synergize with ADP-ribose in the activation of TRPM2 channels. Moll Cell 18: 61-69, 2005.
58. Krippeit-Drews P, Kramer C, Welker S, Lang F, Ammon HP, and Drews G. Interference of H2O2 with stimulus-secretion coupling in mouse pancreatic beta-cells. J Physiol 514: 471-481, 1999.
59. Kubisch HM, Wang J, Luche R, Carlson E, Bray TM, Epstein CJ, and Phillips JP. Transgenic copper=zinc super-oxide dismutase modulates susceptibility to type I diabetes. Proc Natl Acad Sci USA 91: 9956-9959, 1994.
60. Lacraz G, Figeac F, Movassat J, Kassis N, Coulaud J, Ga-linier A, Leloup C, Bailbé D, Homo-Delarche F, and Portha B. Diabetic beta-cells can achieve self-protection against oxidative stress through an adaptive up-regulation of their antioxidant defenses. PLoS One 4: e6500, 2009.
61. Leloup C, Magnan C, Benani A, Bonnet E, Alquier T, Offer G, Carriere A, Périquet A, Fernandez Y, Ktorza A, Casteilla L, and Pénicaud L. Mitochondrial reactive oxygen species are required for hypothalamic glucose sensing. Diabetes 55: 2084-2090, 2006.
62. Leloup C, Tourrel-Cuzin C, Magnan C, Karaca M, Castel J, Carneiro L, Colombani AL, Ktorza A, Casteilla L, and Pé-nicaud L. Mitochondrial reactive oxygen species are obligatory signals for glucose-induced insulin secretion. Diabetes 58: 673-681, 2009.
63. Lenzen S, Drinkgern J, and Tiedge M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic Biol Med 20: 463-466, 1996.
64. Lin Y, Berg AH, Iyengar P, Lam TK, Giacca A, Combs TP, Rajala MW, Du X, Rollman B, Li W, Hawkins M, Barzilai N, Rhodes CJ, Fantus IG, Brownlee M, and Scherer PE. The hyperglycemia-induced inflammatory response in adipo-cytes: the role of reactive oxygen species. J Biol Chem 280: 4617-4626, 2005.
65. Maechler P, Carobbio S, and Rubi B. In beta-cells, mitochondria integrate and generate metabolic signals controlling insulin secretion. Int J Biochem Cell Biol 38: 696-709, 2006.
66. Maechler P, Jornot L, and Wollheim CB. Hydrogen peroxide alters mitochondrial activation and insulin secretion in pancreatic beta cells. J Biol Chem 24: 27905-27913, 1999.
67. Malorni W, Campesi I, Straface E, Vella S, and Franconi F. Redox features of the cell: a gender perspective. Antioxid Redox Signal 9: 1779-1801, 2007.
68. Martens GA, Cai Y, Hinke S, Stangé G, Van de Casteele M, and Pipeleers D. Glucose suppresses superoxide generation in metabolically responsive pancreatic b cells. J Biol Chem 280: 20389-20396, 2005.
69. Mattiasson G, Shamloo M, Gido G, Mathi K, Tomasevic G, Yi S, Warden CH, Castilho RF, Melcher T, Gonzalez-Zulueta M, Nikolich K, and Wieloch T. Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat Med 9: 1062-1068, 2003.
70. Maulik N. Redox signaling of angiogenesis Antioxid Redox Signal 4: 805-815, 2002.
71. Mehta SL and Li PA. Neuroprotective role of mitochondrial uncoupling protein 2 in cerebral stroke. J Cereb Blood Flow Metab 29: 1069-1078, 2009.
72. Migliaccio E, Giorgio M, and Pelicci PG. Apoptosis and aging: role of p66Shc redox protein. Antioxid Redox Signal 8: 600-608, 2006.
73. Miller EW, Dickinson BC, and Chang CJ. Aquaporin-3 mediates hydrogen peroxide uptake to regulate downstream intracellular signaling. Proc Natl Acad Sci USA 107: 15681-15686, 2010.
74. Mobbs CV, Isoda F, Makimura H, Mastaitis J, Mizuno T, Shu IW, Yen K, and Yang XJ. Impaired glucose signaling as a cause of obesity and the metabolic syndrome: the glu-coadipostatic hypothesis. Physiol Behav 85: 3-23, 2005.
75. Mountjoy PD and Rutter GA. Glucose sensing by hypo-thalamic neurones and pancreatic islet cells: ample evidence for common mechanisms? Exp Physiol 92: 311-319, 2007.
76. Nègre-Salvayre A, Hirtz C, Carrera G, Cazenave R, Troly M, Salvayre R, Pénicaud L, and Casteilla L. A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation. FASEB J 11: 809-815, 1997.
77. Nemoto S, Takeda K, Yu ZX, Ferrans VJ, and Finkel T. Role for mitochondrial oxidants as regulators of cellular metabolism. Mol Cell Biol 20: 7311-7318, 2000.
78. Pani G, Koch OR, and Galeotti T. The p53-p66shc-Manganese Superoxide Dismutase (MnSOD) network: a mitochondrial intrigue to generate reactive oxygen species. Int J Biochem Cell Biol 41: 1002-1005, 2009.
79. Páramo B, Hernández-Fonseca K, Estrada-Sánchez AM, Jiménez N, Hernández-Cruz A, and Massieu L. Pathways involved in the generation of reactive oxygen and nitrogen species during glucose deprivation and its role on the death of cultured hippocampal neurons. Neuroscience 167: 1057- 1069, 2010.
80. Parker N, Vidal-Puig AJ, Azzu V, and Brand MD. Dysre-gulation of glucose homeostasis in nicotinamide nucleotide transhydrogenase knockout mice is independent of uncoupling protein 2. Biochim Biophys Acta 1787: 1451-1457, 2009.
81. Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang CY, Xu C, Vianna CR, Balthasar N, Lee CE, Elmquist JK, Cowley MA, and Lowell BB. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449: 228-232, 2007.
82. Pedersen A, Karlsson GB, and Rydström J. Proton-translocating transhydrogenase: an update of unsolved and controversial issues. J Bioenerg Biomembr 40: 463-473, 2008.
83. Pénicaud L, Leloup C, Fioramonti X, Lorsignol A, and Benani A. Brain glucose sensing: a subtle mechanism. Curr Opin Clin Nutr Metab Care, 9: 458-62, 2006.
84. Pi J, Bai Y, Daniel KW, Liu D, Lyght O, Edelstein D, Brownlee M, Corkey BE, and Collins S. Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic b-cell function. Endocrinology 150: 3040-3048, 2009.
85. Pi J, Bai Y, Zhang Q, Wong V, Floering LM, Daniel K, Reece JM, Deeney JT, Andersen ME, Corkey BE, and Collins S. Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes 56: 1783-1791, 2007.
86. Planat-Benard V, Silvestre JS, Cousin B, André M, Nibbe-link M, Tamarat R, Clergue M, Manneville C, Saillan-Barreau C, Duriez M, Tedgui A, Levy B, Pénicaud L, and Casteilla L. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation 109: 656-663, 2004.
87. Produit-Zengaffinen N, Davis-Lameloise N, Perreten H, Bécard D, Gjinovci A, Keller PA, Wollheim CB, Herrera P, Muzzin P, and Assimacopoulos-Jeannet F. Increasing uncoupling protein-2 in pancreatic beta cells does not alter glucose-induced insulin secretion but decreases production of reactive oxygen species. Diabetologia 50: 84-93, 2007.
88. Qian F, Huang P, Ma L, Kutznetsov A, Tamarina N, and Philipson LH. TRP genes: candidates for non-selective cation channels and store-operated channels in insulin-secreting cells. Diabetes 51: S183-S189, 2002.
89. Ranieri SC, Fusco S, Panieri E, Labate V, Mele M, Tesori V, Ferrara AM, Maulucci G, De Spirito M, Martorana GE, Galeotti T, and Pani G. Mammalian life-span determinant p66shcA mediates obesity-induced insulin resistance. Proc Natl Acad Sci USA 107: 13420-13425, 2010.
90. Rhee SG. H2O2, a necessary evil for cell. Science, 312: 1882- 3, 2006.
91. Richard D, Clavel S, Huang Q, Sanchis D, and Ricquier D. Uncoupling protein 2 in the brain: distribution and function. Biochem Soc Trans 29: 812-817, 2001.
92. Rorsman P. The pancreatic beta-cell as a fuel sensor: an electrophysiologist's viewpoint. Diabetologia 40: 487-495, 1997.
93. Saillan-Barreau C, Tabbakh O, Chavoin JP, Casteilla L, and Pénicaud L. Site specific alterations of adipose tissue mitochondria in 3'-azido-3'-deoxythymidine (AZT)-treated rats: an early stage in lipodystrophy? Drug-specific effect of nelfinavir and stavudine on primary culture of human preadipocytes. J Acquir Immune Defic Syndr 48: 20-25, 2008.
94. Sakai K, Matsumoto K, Nishikawa T, Suefuji M, Nakamaru K, Hirashima Y, Kawashima J, Shirotani T, Ichinose K, Brownlee M, and Araki E. Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic b-cells. Bio-chem Biophys Res Com 300: 216-222, 2003.
95. St. Pierre J, Buckingham JA, Roebuck SJ, and Brand MD. Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem 277: 44784-44790, 2002.
96. Schwartz MW, Woods SC, Porte D Jr., Seeley RJ, and Ba-skin DG. Central nervous system control of food intake. Nature 404: 661-671, 2000.
97. Seeley RJ and York DA. Fuel sensing and the central nervous system (CNS): implications for the regulation of energy balance and the treatment for obesity. Obes Rev 6: 259-265, 2005.
98. Singh P, Jain A, and Kaur G. Impact of hypoglycemia and diabetes on CNS: correlation of mitochondrial oxidative stress with DNA damage. Mol Cell Biochem 260: 153-159, 2004.
99. Thorens B. Glucose sensing and the pathogenesis of obesity and type 2 diabetes. Int J Obes (Lond) 32: S62-S71, 2008.
100. Tiedge M, Lortz S, Drinkgern J, and Lenzen S. Relation between antioxidant enzyme gene expression and anti-oxidative defense status of insulin-producing cells. Diabetes 46: 1733-1742, 1997.
101. Togashi K, Hara Y, Tominaga T, Higashi T, Konishi Y, Mori Y, and Tominaga M. TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion. EMBO J 25: 1804-1815, 2006.
102. Tran TT, Yamamoto Y, Gesta S, and Kahn CR. Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab 7: 410-420, 2008.
103. Tsubouchi H, Inoguchi T, Inuo M, Kakimoto M, Sonta T, Sonoda N, Sasaki S, Kobayashi K, Sumimoto H, and Na-wata H. Sulfonylurea as well as elevated glucose levels stimulate reactive oxygen species production in the pancreatic beta-cell line, MIN6-a role of NAD(P)H oxidase in beta-cells. Biochem Biophys Res Commun 326: 60-65, 2005.
104. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 552: 335-344, 2003.
105. Wang P, Mariman E, Renes J, and Keijer J. The secretory function of adipocytes in the physiology of white adipose tissue. J Cell Physiol 216: 3-13, 2008.
106. Wilson-Fritch L, Burkart A, Bell G, Mendelson K, Leszyk J, Nicoloro S, Czech M, and Corvera S. Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone. Mol Cell Biol 23: 1085-1094, 2003.
107. Wilson-Fritch L, Nicoloro S, Chouinard M, Lazar MA, Chui PC, Leszyk J, Straubhaar J, Czech MP, and Corvera S. Mi-tochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest 114: 1281-1289, 2004.
108. Wood IS, de Heredia FP, Wang B, and Trayhurn P. Cellular hypoxia and adipose tissue dysfunction in obesity. Proc Nutr Soc 68: 370-377, 2009.
109. Woods SC, Schwartz MW, Baskin DG, and Seeley RJ. Food intake and the regulation of body weight. Annu Rev Psychol 51: 255-277, 2000.
110. Yamamoto M, Yamato E, Toyoda S, Tashiro F, Ikegami H, Yodoi J, and Miyazaki J. Transgenic expression of antioxi-dant protein thioredoxin in pancreatic beta cells prevents progression of type 2 diabetes mellitus. Antioxid Redox Signal 10: 43-49, 2008.
111. Yang XJ, Kow LM, Funabashi T, and Mobbs CV. Hy-pothalamic glucose sensor: similarities to and differences from pancreatic beta-cell mechanisms. Diabetes 48: 1763-1772, 1999.
112. Zhang CY, Parton LE, Ye CP, Krauss S, Shen R, Lin CT, Porco JA Jr., and Lowell BB. Genipin inhibits UCP2-medi-ated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets. Cell Metab 3: 417-427, 2006.
113. Zhou H, Zhao J, and Zhang X. Inhibition of uncoupling protein 2 by genipin reduces insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Arch Biochem Biophys 486: 88-93, 2009.