Mechanisms in endocrinology: Hypothalamic inflammation and nutrition

European Journal of Endocrinology

Volumn 175, Issue 3, 2016, Pages R97-R105

  Araujo, Eliana P ^a   Moraes, Juliana C ^a   Cintra, Dennys E ^a   Velloso, Licio A ^a  

^a UNIVERSITY OF CAMPINAS   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFLAMMATORY AGENT; BEHENIC ACID; FRACTALKINE; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; JANUS KINASE 2; LEPTIN; LINOLENIC ACID; OLEIC ACID; POLYUNSATURATED FATTY ACID; PROTEIN; PROTEIN MCR4; SATURATED FATTY ACID; STEARIC ACID; TOLL LIKE RECEPTOR 4; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNSATURATED FATTY ACID;

ANTIINFLAMMATORY ACTIVITY; BODY MASS; CARDIOVASCULAR DISEASE; CYTOKINE RELEASE; DIET INDUCED OBESITY; ENDOPLASMIC RETICULUM STRESS; ENERGY EXPENDITURE; FAT INTAKE; FOOD INTAKE; HYPERLEPTINEMIA; HYPOTHALAMIC INFLAMMATION; HYPOTHALAMUS DISEASE; MICROENVIRONMENT; NERVE CELL; NONHUMAN; NUTRITION; PRIORITY JOURNAL; PROTEIN HOMEOSTASIS; REVIEW; SIGNAL TRANSDUCTION; HUMAN; HYPOTHALAMUS; INFLAMMATION; INSULIN RESISTANCE; NUTRITIONAL STATUS; OBESITY; PATHOPHYSIOLOGY; PHYSIOLOGY;

HUMANS; HYPOTHALAMUS; INFLAMMATION; INSULIN RESISTANCE; NEURONS; NUTRITIONAL STATUS; OBESITY;

EID: 84981745076     PISSN: 08044643     EISSN: 1479683X     Source Type: Journal    
DOI: 10.1530/EJE-15-1207     Document Type: Review

References (82)

1. Morton GJ, Cummings DE, Baskin DG, Barsh GS & Schwartz MW. Central nervous system control of food intake and body weight. Nature 2006 443 289-295. (doi:10.1038/nature05026)
2. Woods SC, Schwartz MW, Baskin DG & Seeley RJ. Food intake and the regulation of body weight. Annual Review of Psychology 2000 51 255-277. (doi:10.1146/annurev.psych.51.1.255)
3. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ & Baskin DG. Central nervous system control of food intake. Nature 2000 404 661-671. (doi:10.1038/35007534)
4. Gautron L & Elmquist JK. Sixteen years and counting: an update on leptin in energy balance. Journal of Clinical Investigation 2011 121 2087-2093. (doi:10.1172/JCI45888)
5. Hussain SS & Bloom SR. The regulation of food intake by the gutbrain axis: implications for obesity. International Journal of Obesity 2013 37 625-633. (doi:10.1038/ijo.2012.93)
6. Myers MG Jr, Munzberg H, Leinninger GM & Leshan RL. The geometry of leptin action in the brain: more complicated than a simple ARC. Cell Metabolism 2009 9 117-123. (doi:10.1016/j.cmet.2008.12.001)
7. Lam TK, Schwartz GJ & Rossetti L. Hypothalamic sensing of fatty acids. Nature Neuroscience 2005 8 579-584. (doi:10.1038/nn1456)
8. Velloso LA & Schwartz MW. Altered hypothalamic function in dietinduced obesity. International Journal of Obesity 2011 35 1455-1465. (doi:10.1038/ijo.2011.56)
9. Velloso LA, Folli F & Saad MJ. TLR4 at the crossroads of nutrients, gut microbiota, and metabolic inflammation. Endocrine Reviews 2015 36 245-271. (doi:10.1210/er.2014-1100)
10. Kalin S, Heppner FL, Bechmann I, Prinz M, Tschop MH & Yi CX. Hypothalamic innate immune reaction in obesity. Nature Reviews Endocrinology 2015 11 339-351. (doi:10.1038/nrendo.2015.48)
11. Myles IA. Fast food fever: reviewing the impacts of the Western diet on immunity. Nutrition Journal 2014 13 61. (doi:10.1186/1475-2891-13-61)
12. Mente A, de Koning L, Shannon HS & Anand SS. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Archives of Internal Medicine 2009 169 659-669. (doi:10.1001/archinternmed.2009.38)
13. De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, Boschero AC, Saad MJ & Velloso LA. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 2005 146 4192-4199. (doi:10.1210/en.2004-1520)
14. Zhang X, Zhang G, Zhang H, Karin M, Bai H & Cai D. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 2008 135 61-73. (doi:10.1016/j.cell.2008.07.043)
15. Milanski M, Degasperi G, Coope A, Morari J, Denis R, Cintra DE, Tsukumo DM, Anhe G, Amaral ME, Takahashi HK et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. Journal of Neuroscience: The Official Journal of the Society for Neuroscience 2009 29 359-370. (doi:10.1523/JNEUROSCI.2760-08.2009)
16. Ozcan L, Ergin AS, Lu A, Chung J, Sarkar S, Nie D, Myers MG Jr & Ozcan U. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metabolism 2009 9 35-51. (doi:10.1016/j.cmet.2008.12.004)
17. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR et al. Obesity is associated with hypothalamic injury in rodents and humans. Journal of Clinical Investigation 2012 122 153-162. (doi:10.1172/JCI59660)
18. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L & Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994 372 425-432. (doi:10.1038/372425a0)
19. Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, Lubina JA, Patane J, Self B, Hunt P et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999 282 1568-1575. (doi:10.1001/jama.282.16.1568)
20. Hukshorn CJ, Saris WH, Westerterp-Plantenga MS, Farid AR, Smith FJ & Campfield LA. Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. Journal of Clinical Endocrinology & Metabolism 2000 85 4003-4009.
21. Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB & Flier JS. Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nature Medicine 1995 1 1311-1314.
22. Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH, Lynn RB, Zhang PL, Sinha MK & Considine RV. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996 348 159-161. (doi:10.1016/S0140-6736(96)03173-X)
23. Arch JR, Stock MJ & Trayhurn P. Leptin resistance in obese humans: does it exist and what does it mean? International Journal of Obesity and Related Metabolic Disorders 1998 22 1159-1163. (doi:10.1038/sj.ijo.0800779)
24. Myers MG Jr, Leibel RL, Seeley RJ & Schwartz MW. Obesity and leptin resistance: distinguishing cause from effect. Trends in Endocrinology & Metabolism 2010 21 643-651. (doi:10.1016/j.tem.2010.08.002)
25. Thaler JP, Guyenet SJ, Dorfman MD, Wisse BE & Schwartz MW. Hypothalamic inflammation: marker or mechanism of obesity pathogenesis? Diabetes 2013 62 2629-2634. (doi:10.2337/db12-1605)
26. Farooqi IS & O'Rahilly S. Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nature Clinical Practice Endocrinology & Metabolism 2008 4 569-577.
27. Bjorbaek C, El-Haschimi K, Frantz JD & Flier JS. The role of SOCS-3 in leptin signaling and leptin resistance. Journal of Biological Chemistry 1999 274 30059-30065. (doi:10.1074/jbc.274.42.30059)
28. Mori H, Hanada R, Hanada T, Aki D, Mashima R, Nishinakamura H, Torisu T, Chien KR, Yasukawa H & Yoshimura A. Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nature Medicine 2004 10 739-743. (doi:10.1038/nm1071)
29. Howard JK, Cave BJ, Oksanen LJ, Tzameli I, Bjorbaek C & Flier JS. Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3. Nature Medicine 2004 10 734-738. (doi:10.1038/nm1072)
30. Munzberg H & Myers MG Jr. Molecular and anatomical determinants of central leptin resistance. Nature Neuroscience 2005 8 566-570. (doi:10.1038/nn1454)
31. Morari J, Anhe GF, Nascimento LF, de Moura RF, Razolli D, Solon C, Guadagnini D, Souza G, Mattos AH, Tobar N et al. Fractalkine (CX3CL1) is involved in the early activation of hypothalamic inflammation in experimental obesity. Diabetes 2014 63 3770-3784. (doi:10.2337/db13-1495)
32. Hickman SE & El Khoury J. Mechanisms of mononuclear phagocyte recruitment in Alzheimer's disease. CNS & Neurological Disorders - Drug Targets 2010 9 168-173.
33. Aguzzi A, Barres BA & Bennett ML. Microglia: scapegoat, saboteur, or something else? Science 2013 339 156-161. (doi:10.1126/science.1227901)
34. Benoit SC, Kemp CJ, Elias CF, Abplanalp W, Herman JP, Migrenne S, Lefevre AL, Cruciani-Guglielmacci C, Magnan C, Yu F et al. Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents. Journal of Clinical Investigation 2009 119 2577-2589. (doi:10.1172/JCI36714)
35. Milanski M, Arruda AP, Coope A, Ignacio-Souza LM, Nunez CE, Roman EA, Romanatto T, Pascoal LB, Caricilli AM, Torsoni MA et al. Inhibition of hypothalamic inflammation reverses diet-induced insulin resistance in the liver. Diabetes 2012 61 1455-1462. (doi:10.2337/db11-0390)
36. Valdearcos M, Robblee MM, Benjamin DI, Nomura DK, Xu AW & Koliwad SK. Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Reports 2014 9 2124-2138. (doi:10.1016/j.celrep.2014.11.018)
37. Fuente-Martin E, Garcia-Caceres C, Diaz F, Argente-Arizon P, Granado M, Barrios V, Argente J & Chowen JA. Hypothalamic inflammation without astrogliosis in response to high sucrose intake is modulated by neonatal nutrition in male rats. Endocrinology 2013 154 2318-2330. (doi:10.1210/en.2012-2196)
38. Xu MX, Yu R, Shao LF, Zhang YX, Ge CX, Liu XM, Wu WY, Li JM & Kong LD. Up-regulated fractalkine (FKN) and its receptor CX3CR1 are involved in fructose-induced neuroinflammation: suppression by curcumin. Brain, Behavior, and Immunity 2016. In press. (doi:10.1016/j.bbi.2016.01.001)
39. Haber S. Effective treatment of obesity produces remission, not cure. International Journal of Obesity 1980 4 265-267.
40. Goodrick GK & Foreyt JP. Why treatments for obesity don't last. Journal of the American Dietetic Association 1991 91 1243-1247.
41. Kraschnewski JL, Boan J, Esposito J, Sherwood NE, Lehman EB, Kephart DK & Sciamanna CN. Long-term weight loss maintenance in the United States. International Journal of Obesity 2010 34 1644-1654. (doi:10.1038/ijo.2010.94)
42. Kalarchian MA, Marcus MD, Courcoulas AP, Cheng Y, Levine MD & Josbeno D. Optimizing long-term weight control after bariatric surgery: a pilot study. Surgery for Obesity and Related Diseases 2012 8 710-715. (doi:10.1016/j.soard.2011.04.231)
43. Morton GJ, Meek TH & Schwartz MW. Neurobiology of food intake in health and disease. Nature Reviews Neuroscience 2014 15 367-378. (doi:10.1038/nrn3745)
44. Moraes JC, Coope A, Morari J, Cintra DE, Roman EA, Pauli JR, Romanatto T, Carvalheira JB, Oliveira AL, Saad MJ et al. High-fat diet induces apoptosis of hypothalamic neurons. PLoS ONE 2009 4 e5045. (doi:10.1371/journal.pone.0005045)
45. Li J, Tang Y & Cai D. IKKbeta/NF-kappaB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes. Nature Cell Biology 2012 14 999-1012. (doi:10.1038/ncb2562)
46. Ignacio-Souza LM, Bombassaro B, Pascoal LB, Portovedo MA, Razolli DS, Coope A, Victorio SC, de Moura RF, Nascimento LF, Arruda AP et al. Defective regulation of the ubiquitin/proteasome system in the hypothalamus of obese male mice. Endocrinology 2014 155 2831-2844. (doi:10.1210/en.2014-1090)
47. Meng Q & Cai D. Defective hypothalamic autophagy directs the central pathogenesis of obesity via the IkappaB kinase beta (IKKbeta)/NF-kappaB pathway. Journal of Biological Chemistry 2011 286 32324-32332. (doi:10.1074/jbc.M111.254417)
48. Powers ET & Balch WE. Diversity in the origins of proteostasis networks - a driver for protein function in evolution. Nature Reviews. Molecular Cell Biology 2013 14 237-248. (doi:10.1038/nrm3542)
49. Tokuriki N & Tawfik DS. Stability effects of mutations and protein evolvability. Current Opinion in Structural Biology 2009 19 596-604. (doi:10.1016/j.sbi.2009.08.003)
50. Broadley SA & Hartl FU. The role of molecular chaperones in human misfolding diseases. FEBS Letters 2009 583 2647-2653. (doi:10.1016/j.febslet.2009.04.029)
51. Balch WE, Morimoto RI, Dillin A & Kelly JW. Adapting proteostasis for disease intervention. Science 2008 319 916-919. (doi:10.1126/science.1141448)
52. Yan J, Zhang H, Yin Y, Li J, Tang Y, Purkayastha S, Li L & Cai D. Obesity- and aging-induced excess of central transforming growth factor-beta potentiates diabetic development via an RNA stress response. Nature Medicine 2014 20 1001-1008. (doi:10.1038/nm.3616)
53. Araujo EP, de Souza CT & Velloso LA. Atypical transforming growth factor-beta signaling in the hypothalamus is linked to diabetes. Nature Medicine 2014 20 985-987. (doi:10.1038/nm.3673)
54. Wolff S, Weissman JS & Dillin A. Differential scales of protein quality control. Cell 2014 157 52-64. (doi:10.1016/j.cell.2014.03.007)
55. Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 2010 140 900-917. (doi:10.1016/j.cell.2010.02.034)
56. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH & Hotamisligil GS. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004 306 457-461. (doi:10.1126/science.1103160)
57. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Gorgun CZ & Hotamisligil GS. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006 313 1137-1140. (doi:10.1126/science.1128294)
58. Coope A, Milanski M, Arruda AP, Ignacio-Souza LM, Saad MJ, Anhe GF & Velloso LA. Chaperone insufficiency links TLR4 protein signaling to endoplasmic reticulum stress. Journal of Biological Chemistry 2012 287 15580-15589. (doi:10.1074/jbc.M111.315218)
59. Cnop M, Foufelle F & Velloso LA. Endoplasmic reticulum stress, obesity and diabetes. Trends in Molecular Medicine 2012 18 59-68. (doi:10.1016/j.molmed.2011.07.010)
60. Nath D & Shadan S. The ubiquitin system. Nature 2009 458 421. (doi:10.1038/458421a)
61. Pickart CM & Fushman D. Polyubiquitin chains: polymeric protein signals. Current Opinion in Chemical Biology 2004 8 610-616. (doi:10.1016/j.cbpa.2004.09.009)
62. Nakatogawa H, Suzuki K, Kamada Y & Ohsumi Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nature Reviews. Molecular Cell Biology 2009 10 458-467. (doi:10.1038/nrm2708)
63. Portovedo M, Ignacio-Souza LM, Bombassaro B, Coope A, Reginato A, Razolli DS, Torsoni MA, Torsoni AS, Leal RF, Velloso LA et al. Saturated fatty acids modulate autophagy's proteins in the hypothalamus. PLoS ONE 2015 10 e0119850. (doi:10.1371/journal.pone.011985)
64. Kaushik S, Rodriguez-Navarro JA, Arias E, Kiffin R, Sahu S, Schwartz GJ, Cuervo AM & Singh R. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metabolism 2011 14 173-183. (doi:10.1016/j.cmet.2011.06.008)
65. Schneeberger M, Altirriba J, Garcia A, Esteban Y, Castano C, Garcia-Lavandeira M, Alvarez CV, Gomis R & Claret M. Deletion of miRNA processing enzyme Dicer in POMC-expressing cells leads to pituitary dysfunction, neurodegeneration and development of obesity. Molecular Metabolism 2012 2 74-85. (doi:10.1016/j.molmet.2012.10.001)
66. Kaushik S, Arias E, Kwon H, Lopez NM, Athonvarangkul D, Sahu S, Schwartz GJ, Pessin JE & Singh R. Loss of autophagy in hypothalamic POMC neurons impairs lipolysis. EMBO Reports 2012 13 258-265. (doi:10.1038/embor.2011.260)
67. Le Stunff H, Coant N, Migrenne S & Magnan C. Targeting lipid sensing in the central nervous system: new therapy against the development of obesity and type 2 diabetes. Expert Opinion on Therapeutic Targets 2013 17 545-555. (doi:10.1517/14728222.2013.768233)
68. Bjerregaard P, Mulvad G & Pedersen HS. Cardiovascular risk factors in Inuit of Greenland. International Journal of Epidemiology 1997 26 1182-1190. (doi:10.1093/ije/26.6.1182)
69. Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, Elwood PC & Deadman NM. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989 2 757-761. (doi:10.1016/S0140-6736(89)90828-3)
70. Fischer S & Weber PC. Prostaglandin I3 is formed in vivo in man after dietary eicosapentaenoic acid. Nature 1984 307 165-168. (doi:10.1038/307165a0)
71. Schmitz G & Ecker J. The opposing effects of n-3 and n-6 fatty acids. Progress in Lipid Research 2008 47 147-155. (doi:10.1016/j.plipres.2007.12.004)
72. Serhan CN, Chiang N & Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nature Reviews Immunology 2008 8 349-361. (doi:10.1038/nri2294)
73. Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM & Olefsky JM. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010 142 687-698. (doi:10.1016/j.cell.2010.07.041)
74. Delerive P, Gervois P, Fruchart JC & Staels B. Induction of IkappaBalpha expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-alpha activators. Journal of Biological Chemistry 2000 275 36703-36707. (doi:10.1074/jbc.M004045200)
75. Taouis M, Dagou C, Ster C, Durand G, Pinault M & Delarue J. N-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle. American Journal of Physiology: Endocrinology and Metabolism 2002 282 E664-E671. (doi:10.1152/ajpendo.00320.2001)
76. Sekiya M, Yahagi N, Matsuzaka T, Najima Y, Nakakuki M, Nagai R, Ishibashi S, Osuga J, Yamada N & Shimano H. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 2003 38 1529-1539. (doi:10.1053/jhep.2003.09028)
77. Oh da Y, Walenta E, Akiyama TE, Lagakos WS, Lackey D, Pessentheiner AR, Sasik R, Hah N, Chi TJ, Cox JM et al. A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice. Nature Medicine 2014 20 942-947. (doi:10.1038/nm.3614)
78. Cintra DE, Ropelle ER, Moraes JC, Pauli JR, Morari J, Souza CT, Grimaldi R, Stahl M, Carvalheira JB, Saad MJ et al. Unsaturated fatty acids revert diet-induced hypothalamic inflammation in obesity. PLoS ONE 2012 7 e30571. (doi:10.1371/journal.pone.0030571)
79. Nascimento LF, Souza GF, Morari J, Barbosa GO, Solon C, Moura RF, Victorio SC, Ignacio-Souza LM, Razolli DS, Carvalho HF et al. Omega-3 fatty acids induce neurogenesis of predominantly POMC-expressing cells in the hypothalamus. Diabetes 2016 65 673-686. (doi:10.2337/db15-0008)
80. Pencea V, Bingaman KD, Wiegand SJ & Luskin MB. Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. Journal of Neuroscience 2001 21 6706-6717.
81. Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, Li B, Liu G & Cai D. Hypothalamic programming of systemic ageing involving IKKbeta, NF-kappaB and GnRH. Nature 2013 497 211-216. (doi:10.1038/nature12143)
82. 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. Nature Medicine 2005 11 320-327. (doi:10.1038/nm1201)