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Time-course study of high fat diet induced alterations in spatial memory, hippocampal JNK, P38, ERK and Akt activity

  • Zahra Abbasnejad
  • Behzad Nasseri
  • Homeira Zardooz
  • Rasoul GhasemiEmail author
Original Article
  • 35 Downloads

Abstract

Consumption of high fat diet (HFD) is a health concern in modern societies, which participate in wide range of diseases. One underlying mechanism in the HFD mediated pathologies is disruption of insulin signaling activity. It is believed that HFD activates several stress signaling molecules such as MAPKs signaling pathway and these molecules participate in harmful effects in different cell populations including hippocampal cells. However, the activity of MAPKs signaling molecules are time dependent, even causing some opposing effects. Given that, MAPKs activity fluctuate with time of stress, there is less cleared how different lengths of HFD consumption can affect hippocampal MAPK. To test how duration of HFD consumption affect hippocampal MAPKs and insulin signaling activity and animal’s cognitive function, rats were fed with HFD for different lengths (up to 6 months) and after each point spatial memory performances of animals was tested, then the peripheral indices of insulin resistance and hippocampal MAPKs and insulin signaling activity was evaluated. Results showed that while different time courses of HFD, up to 6 months, did not bring about significant spatial memory impairment, meanwhile the peripheral insulin sensitivity as well as hippocampal insulin and MAPKs signaling showed significant fluctuations during the different time courses of high fat diet regime. These results showed that neuronal responses to HFD is not constant and differ in a time-dependent manner, it seems that in acute phase molecular responses aimed to compensate the HFD stress but in chronic states these responses failed and devastating effects of stress began.

Keywords

High-fat diet Insulin resistance MAPKs Akt Spatial memory 

Notes

Acknowledgments

This article has been extracted from the thesis written by Mrs. “Zahra Abbasnejad” in School of Medicine Shahid Beheshti University of Medical Sciences Tehran, Iran (Registration No: 432).

Compliance with ethical standards

Disclosure of interest

The authors report no conflict of interest.

References

  1. Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, Hemmings BA (1996) Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15(23):6541–6551PubMedPubMedCentralCrossRefGoogle Scholar
  2. Arnold SE, Lucki I, Brookshire BR, Carlson GC, Browne CA, Kazi H, Bang S, Choi BR, Chen Y, McMullen MF, Kim SF (2014) High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice. Neurobiol Dis 67:79–87PubMedPubMedCentralCrossRefGoogle Scholar
  3. Austin GL, Ogden LG, Hill JO (2011) Trends in carbohydrate, fat, and protein intakes and association with energy intake in normal-weight, overweight, and obese individuals: 1971-2006. Am J Clin Nutr 93(4):836–843PubMedCrossRefGoogle Scholar
  4. Avruch J (2007) MAP kinase pathways: the first twenty years. Biochim Biophys Acta 1773(8):1150–1160PubMedCrossRefGoogle Scholar
  5. Beguin PC, Belaidi E, Godin-Ribuot D, Levy P, Ribuot C (2007) Intermittent hypoxia-induced delayed cardioprotection is mediated by PKC and triggered by p38 MAP kinase and Erk1/2. J Mol Cell Cardiol 42(2):343–351PubMedCrossRefGoogle Scholar
  6. Biessels GJ, Reagan LP (2015) Hippocampal insulin resistance and cognitive dysfunction. Nat Rev Neurosci 16(11):660–671PubMedCrossRefGoogle Scholar
  7. Boitard C, Etchamendy N, Sauvant J, Aubert A, Tronel S, Marighetto A, Layé S, Ferreira G (2012) Juvenile, but not adult exposure to high-fat diet impairs relational memory and hippocampal neurogenesis in mice. Hippocampus 22(11):2095–2100CrossRefGoogle Scholar
  8. Boitard C, Cavaroc A, Sauvant J, Aubert A, Castanon N, Laye S et al (2014) Impairment of hippocampal-dependent memory induced by juvenile high-fat diet intake is associated with enhanced hippocampal inflammation in rats. Brain Behav Immun 40:9–17PubMedCrossRefGoogle Scholar
  9. Bonen A, Jain SS, Snook LA, Han X-X, Yoshida Y, Buddo KH, Lally JS, Pask ED, Paglialunga S, Beaudoin MS, Glatz JFC, Luiken JJFP, Harasim E, Wright DC, Chabowski A, Holloway GP (2015) Extremely rapid increase in fatty acid transport and intramyocellular lipid accumulation but markedly delayed insulin resistance after high fat feeding in rats. Diabetologia 58(10):2381–2391PubMedCrossRefGoogle Scholar
  10. Buettner R, Scholmerich J, Bollheimer LC (2007) High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring) 15(4):798–808CrossRefGoogle Scholar
  11. Calvo-Ochoa E, Hernández-Ortega K, Ferrera P, Morimoto S, Arias C (2014) Short-term high-fat-and-fructose feeding produces insulin signaling alterations accompanied by neurite and synaptic reduction and astroglial activation in the rat hippocampus. J Cereb Blood Flow Metab 34(6):1001–1008PubMedPubMedCentralCrossRefGoogle Scholar
  12. Crowe DL, Shemirani B (2000) The transcription factor ATF-2 inhibits extracellular signal regulated kinase expression and proliferation of human cancer cells. Anticancer Res 20(5a):2945–2949PubMedGoogle Scholar
  13. de la Monte SM (2012) Triangulated mal-signaling in Alzheimer's disease: roles of neurotoxic ceramides, ER stress, and insulin resistance reviewed. J Alzheimers Dis 30(Suppl 2):S231–S249PubMedPubMedCentralCrossRefGoogle Scholar
  14. Engelman JA, Berg AH, Lewis RY, Lisanti MP, Scherer PE (2000) Tumor necrosis factor α-mediated insulin resistance, but not dedifferentiation, is abrogated by MEK1/2 inhibitors in 3T3-L1 adipocytes. Mol Endocrinol 14(10):1557–1569PubMedGoogle Scholar
  15. Freeman LR, Haley-Zitlin V, Rosenberger DS, Granholm AC (2014) Damaging effects of a high-fat diet to the brain and cognition: a review of proposed mechanisms. Nutr Neurosci 17(6):241–251PubMedCrossRefGoogle Scholar
  16. Ghasemi R, Haeri A, Dargahi L, Mohamed Z, Ahmadiani A (2013) Insulin in the brain: sources, localization and functions. Mol Neurobiol 47(1):145–171PubMedCrossRefGoogle Scholar
  17. Ghasemi R, Zarifkar A, Rastegar K, Maghsoudi N, Moosavi M (2014) Repeated intra-hippocampal injection of beta-amyloid 25-35 induces a reproducible impairment of learning and memory: considering caspase-3 and MAPKs activity. Eur J Pharmacol 726:33–40PubMedCrossRefGoogle Scholar
  18. Greenwood CE, Winocur G (1990) Learning and memory impairment in rats fed a high saturated fat diet. Behav Neural Biol 53(1):74–87PubMedCrossRefGoogle Scholar
  19. Greenwood CE, Winocur G (1996) Cognitive impairment in rats fed high-fat diets: a specific effect of saturated fatty-acid intake. Behav Neurosci 110(3):451–459PubMedCrossRefGoogle Scholar
  20. Gual P, Le Marchand-Brustel Y, Tanti JF (2005) Positive and negative regulation of insulin signaling through IRS-1 phosphorylation. Biochimie 87(1):99–109PubMedCrossRefGoogle Scholar
  21. Harika RK, Eilander A, Alssema M, Osendarp SJ, Zock PL (2013) Intake of fatty acids in general populations worldwide does not meet dietary recommendations to prevent coronary heart disease: a systematic review of data from 40 countries. Ann Nutr Metab 63(3):229–238PubMedCrossRefGoogle Scholar
  22. Hemmati F, Ghasemi R, Mohamed Ibrahim N, Dargahi L, Mohamed Z, Raymond AA, Ahmadiani A (2014) Crosstalk between insulin and toll-like receptor signaling pathways in the central nervous system. Mol Neurobiol 50(3):797–810PubMedCrossRefGoogle Scholar
  23. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K et al (2002) A central role for JNK in obesity and insulin resistance. Nature 420(6913):333–336PubMedCrossRefGoogle Scholar
  24. Hwang LL, Wang CH, Li TL, Chang SD, Lin LC, Chen CP, Chen CT, Liang KC, Ho IK, Yang WS, Chiou LC (2010) Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice. Obesity (Silver Spring) 18(3):463–469CrossRefGoogle Scholar
  25. Jurdak N, Kanarek RB (2009) Sucrose-induced obesity impairs novel object recognition learning in young rats. Physiol Behav 96(1):1–5PubMedCrossRefGoogle Scholar
  26. Karbaschi R, Sadeghimahalli F, Zardooz H (2016) Maternal high-fat diet inversely affects insulin sensitivity in dams and young adult male rat offspring. J Zhejiang Univ Sci B 17(9):728–732PubMedPubMedCentralCrossRefGoogle Scholar
  27. Karimi SA, Salehi I, Komaki A, Sarihi A, Zarei M, Shahidi S (2013) Effect of high-fat diet and antioxidants on hippocampal long-term potentiation in rats: an in vivo study. Brain Res 1539:1–6PubMedCrossRefGoogle Scholar
  28. Knight EM, Martins IV, Gumusgoz S, Allan SM, Lawrence CB (2014) High-fat diet-induced memory impairment in triple-transgenic Alzheimer's disease (3xTgAD) mice is independent of changes in amyloid and tau pathology. Neurobiol Aging 35(8):1821–1832PubMedPubMedCentralCrossRefGoogle Scholar
  29. Komaki A, Karimi SA, Salehi I, Sarihi A, Shahidi S, Zarei M (2015) The treatment combination of vitamins E and C and astaxanthin prevents high-fat diet induced memory deficits in rats. Pharmacol Biochem Behav 131:98–103PubMedCrossRefGoogle Scholar
  30. Krishna S, Lin Z, Claire B, Wagner JJ, Harn DH, Pepples LM et al (2016) Time-dependent behavioral, neurochemical, and metabolic dysregulation in female C57BL/6 mice caused by chronic high-fat diet intake. Physiol Behav 157:196–208PubMedPubMedCentralCrossRefGoogle Scholar
  31. Kumar A, Jaggi AS, Sodhi RK, Singh N (2014) Silymarin ameliorates memory deficits and neuropathological changes in mouse model of high-fat-diet-induced experimental dementia. Naunyn Schmiedeberg's Arch Pharmacol 387(8):777–787CrossRefGoogle Scholar
  32. Lavin DN, Joesting JJ, Chiu GS, Moon ML, Meng J, Dilger RN, Freund GG (2011) Fasting induces an anti-inflammatory effect on the neuroimmune system which a high-fat diet prevents. Obesity (Silver Spring) 19(8):1586–1594CrossRefGoogle Scholar
  33. Lee YS, Li P, Huh JY, Hwang IJ, Lu M, Kim JI, Ham M, Talukdar S, Chen A, Lu WJ, Bandyopadhyay GK, Schwendener R, Olefsky J, Kim JB (2011) Inflammation is necessary for long-term but not short-term high-fat diet–induced insulin resistance. Diabetes 60(10):2474–2483PubMedPubMedCentralCrossRefGoogle Scholar
  34. Li F, Omori N, Sato K, Jin G, Nagano I, Manabe Y, Shoji M, Abe K (2002) Coordinate expression of survival p-ERK and proapoptotic cytochrome c signals in rat brain neurons after transient MCAO. Brain Res 958(1):83–88PubMedCrossRefGoogle Scholar
  35. Lindqvist A, Mohapel P, Bouter B, Frielingsdorf H, Pizzo D, Brundin P, Erlanson-Albertsson C (2006) High-fat diet impairs hippocampal neurogenesis in male rats. Eur J Neurol 13(12):1385–1388PubMedCrossRefGoogle Scholar
  36. Liu Z, Patil IY, Jiang T, Sancheti H, Walsh JP, Stiles BL, Yin F, Cadenas E (2015) High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity. PLoS One 10(5):e0128274PubMedPubMedCentralCrossRefGoogle Scholar
  37. Mansouri A, Ridgway LD, Korapati AL, Zhang Q, Tian L, Wang Y, Siddik ZH, Mills GB, Claret FX (2003) Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells. J Biol Chem 278(21):19245–19256PubMedCrossRefGoogle Scholar
  38. Mi Y, Qi G, Fan R, Qiao Q, Sun Y, Gao Y et al (2017) EGCG ameliorates high-fat–and high-fructose–induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF. FASEB J 31(11):4998–5011PubMedCrossRefGoogle Scholar
  39. Moosavi M, Zarifkar AH, Farbood Y, Dianat M, Sarkaki A, Ghasemi R (2014) Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3beta signaling disruption. Eur J Pharmacol 736:107–114PubMedCrossRefGoogle Scholar
  40. Negintaji K, Zarifkar A, Ghasemi R, Moosavi M (2015) Humanin does not protect against STZ-induced spatial memory impairment. J Mol Neurosci 56(2):290–298Google Scholar
  41. Nguyen JC, Ali SF, Kosari S, Woodman OL, Spencer SJ, Killcross AS et al (2017) Western diet chow consumption in rats induces striatal neuronal activation while reducing dopamine levels without affecting spatial memory in the radial arm maze. Front Behav Neurosci 11:22PubMedPubMedCentralCrossRefGoogle Scholar
  42. Oh H, Boghossian S, York DA, Park-York M (2013) The effect of high fat diet and saturated fatty acids on insulin signaling in the amygdala and hypothalamus of rats. Brain Res 1537:191–200PubMedCrossRefGoogle Scholar
  43. Park HR, Park M, Choi J, Park KY, Chung HY, Lee J (2010) A high-fat diet impairs neurogenesis: involvement of lipid peroxidation and brain-derived neurotrophic factor. Neurosci Lett 482(3):235–239PubMedCrossRefGoogle Scholar
  44. Peroval MY, Boyd AC, Young JR, Smith AL (2013) A critical role for MAPK signalling pathways in the transcriptional regulation of toll like receptors. PLoS One 8(2):e51243PubMedPubMedCentralCrossRefGoogle Scholar
  45. Pipatpiboon N, Pratchayasakul W, Chattipakorn N, Chattipakorn SC (2012) PPARγ agonist improves neuronal insulin receptor function in hippocampus and brain mitochondria function in rats with insulin resistance induced by long term high-fat diets. Endocrinology 153(1):329–338PubMedCrossRefGoogle Scholar
  46. Pratchayasakul W, Kerdphoo S, Petsophonsakul P, Pongchaidecha A, Chattipakorn N, Chattipakorn SC (2011) Effects of high-fat diet on insulin receptor function in rat hippocampus and the level of neuronal corticosterone. Life Sci 88(13–14):619–627PubMedCrossRefGoogle Scholar
  47. Price SA, Hounsom L, Purves-Tyson TD, Fernyhough P, Tomlinson DR (2003) Activation of JNK in sensory neurons protects against sensory neuron cell death in diabetes and on exposure to glucose/oxidative stress in vitro. Ann N Y Acad Sci 1010:95–99PubMedCrossRefGoogle Scholar
  48. Rohman A, Triyana K, Sismindari S, Erwanto Y (2012) Differentiation of lard and other animal fats based on triacylglycerols composition and principal component analysis. Int Food Res J 19(2):475–479Google Scholar
  49. Samuel VT, Liu Z-X, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI (2004) Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 279(31):32345–32353PubMedPubMedCentralCrossRefGoogle Scholar
  50. Saurin AT, Martin JL, Heads RJ, Foley C, Mockridge JW, Wright MJ et al (2000) The role of differential activation of p38-mitogen-activated protein kinase in preconditioned ventricular myocytes. FASEB J 14(14):2237–2246PubMedCrossRefGoogle Scholar
  51. Sodhi RK, Singh N (2013) Defensive effect of lansoprazole in dementia of AD type in mice exposed to streptozotocin and cholesterol enriched diet. PLoS One 8(7):e70487PubMedPubMedCentralCrossRefGoogle Scholar
  52. Stanciu M, Wang Y, Kentor R, Burke N, Watkins S, Kress G, Reynolds I, Klann E, Angiolieri MR, Johnson JW, DeFranco DB (2000) Persistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures. J Biol Chem 275(16):12200–12206PubMedCrossRefGoogle Scholar
  53. Stranahan AM, Norman ED, Lee K, Cutler RG, Telljohann RS, Egan JM, Mattson MP (2008) Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus 18(11):1085–1088PubMedPubMedCentralCrossRefGoogle Scholar
  54. Subramaniam S, Unsicker K (2010) ERK and cell death: ERK1/2 in neuronal death. FEBS J 277(1):22–29PubMedCrossRefGoogle Scholar
  55. Sun Y, Liu W-Z, Liu T, Feng X, Yang N, Zhou H-F (2015) Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct 35(6):600–604CrossRefGoogle Scholar
  56. Svensson C, Part K, Kunnis-Beres K, Kaldmae M, Fernaeus SZ, Land T (2011) Pro-survival effects of JNK and p38 MAPK pathways in LPS-induced activation of BV-2 cells. Biochem Biophys Res Commun 406(3):488–492PubMedCrossRefGoogle Scholar
  57. Taniguchi CM, Emanuelli B, Kahn CR (2006) Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 7(2):85–96PubMedCrossRefGoogle Scholar
  58. Tanti JF, Jager J (2009) Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Curr Opin Pharmacol 9(6):753–762PubMedCrossRefGoogle Scholar
  59. Uehling DE, Harris PA (2015) Recent progress on MAP kinase pathway inhibitors. Bioorg Med Chem Lett 25(19):4047–4056PubMedCrossRefGoogle Scholar
  60. Vadiveloo M, Scott M, Quatromoni P, Jacques P, Parekh N (2014) Trends in dietary fat and high-fat food intakes from 1991 to 2008 in the Framingham heart study participants. Br J Nutr 111(4):724–734PubMedCrossRefGoogle Scholar
  61. Wang J, Obici S, Morgan K, Barzilai N, Feng Z, Rossetti L (2001) Overfeeding rapidly induces leptin and insulin resistance. Diabetes 50(12):2786–2791PubMedCrossRefGoogle Scholar
  62. Wang Z, Fan J, Wang J, Li Y, Xiao L, Duan D, Wang Q (2016) Protective effect of lycopene on high-fat diet-induced cognitive impairment in rats. Neurosci Lett 627:185–191PubMedCrossRefGoogle Scholar
  63. Winzell M, Ahrén B (2004) The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 53(Suppl 3):S215–S219PubMedCrossRefGoogle Scholar
  64. Woodie L, Blythe S (2017) The differential effects of high-fat and high-fructose diets on physiology and behavior in male rats. Nutr Neurosci:1–9Google Scholar
  65. Wu JJ, Roth RJ, Anderson EJ, Hong EG, Lee MK, Choi CS, Neufer PD, Shulman GI, Kim JK, Bennett AM (2006) Mice lacking MAP kinase phosphatase-1 have enhanced MAP kinase activity and resistance to diet-induced obesity. Cell Metab 4(1):61–73PubMedCrossRefGoogle Scholar
  66. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270(5240):1326–1331PubMedCrossRefGoogle Scholar
  67. Zare K, Tabatabaei SR, Shahriari A, Jafari RA (2012) The effect of butter oil on avoidance memory in normal and diabetic rats. Iran J Basic Med Sci 15(4):983–989PubMedPubMedCentralGoogle Scholar

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Authors and Affiliations

  1. 1.Neuroscience Research CenterShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of Physiology, Faculty of MedicineShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Neurophysiology Research CenterShahid Beheshti University of Medical SciencesTehranIran

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