Time-course study of high fat diet induced alterations in spatial memory, hippocampal JNK, P38, ERK and Akt activity
- 35 Downloads
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.
KeywordsHigh-fat diet Insulin resistance MAPKs Akt Spatial memory
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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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