Effect of high-fat-fructose diet on synaptic plasticity in hippocampus and lipid profile of blood serum of rat: pharmacological possibilities of affecting risk factors

Open access


The aim of this study was to determine pharmacological possibilities of influencing the risk factors of metabolic syndrome (MetS). Hypertriacylglycerolemic (HTG) rats fed with high-fat-fructose diet (HFFD) were used as a model of the MetS. Wistar rats fed with standard diet were used as negative control group. HTG rats fed with HFFD for 8 weeks were used as positive control group. The effects of atorvastatin and SMe1EC2 were tested. The compounds were administered to the HTG rats after 5 weeks of HFFD, once a day for 3 weeks. After 8 weeks, the blood serum lipid profile and electrophysiology of neurotransmission in hippocampal sections were evaluated in vitro. SMe1EC2 and atorvastatin had a significant effect on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-cholesterol) and atorvastatin had a significant effect on triacylglycerols (TGs). SMe1EC2 improved the long-term potentiation (LTP) course in the hippocampus.

[1] Alfaro F. J.: Lioutas V. A., Pimentel D. A., Chung C. C., Bedoya F., Yoo W. K., Novak V.: Cognitive decline in metabolic syndrome is linked to microstructural white matter abnormalities. J Neurol. 2016;263:2505-2514.

[2] Bezek Š., Paulovičová E., Sotníková R., Navarová J., Gajdošík A, Bauer V., Dřímal J., Nosáľová V., Kyseľová Z.: The effect of novel pyridoindole derivative SMe1EC2 and atorvastatin on selected parameters in hereditary hypertriglyceridemic rats fed high-cholesterol diet. Presented at: International Symposium. Nitric Oxide: From Basic Regulation to Lifestylerelated Diseases; September 16-21, 2009; Tučepi, Croatia.

[3] Cornier M.A., Dabelea D., Hernandez T.L., Lindstrom R.C., Steig A.J., Stob N.R., Van Pelt R.E., Wang H., Eckel R.H.: The metabolic syndrome. Endocr Rev. 2008;29:777-822.

[4] Chukijrungroat N., Khamphaya T., Weerachayaphorn J., Songserm T., Saengsirisuwan V: Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver. Am J Physiol Endocrinol Metab. 2017;313:203-212.

[5] Granholm A., Bimonte-Nelson H. A., Moore A. B., Nelson M. E., Freeman L. R., Sambamurti K.: Effects of a saturated fat and high cholesterol diet on memory and hippocampal morphology in the middle-aged rat. J Alzheimer’s Dis. 2008;14:133–145.

[6] Horáková L., Štolc S.: Antioxidant and pharmacodynamic effects of pyridoindole stobadine. Gen Pharmacol, 1998;30:627–638.

[7] Janczura M., Bochenek G., Nowobilski R., Dropinski J., Kotula-Horowitz K., Laskowicz B., Stanisz A., Lelakowski J., Domagala T.: The relationship of metabolic syndrome with stress, coronary heart disease and pulmonary function - An occupational cohort-based study. PloS One, 2015;10:1-20.

[8] Jia Y-J., Liu J., Guo Y-L., Xu R-X., Sun J., Li J-J.: dyslipidemia in rat fed with high-fat diet is not associated with PCSK9-LDLreceptor pathway but ageing. J Geriatr Cardiol. 2013;10:361-368.

[9] Krishna S., Keralapura M. M., Lin Z., Wagner J. J., de La Serre C. B., Harn D. A., Filipov M. M.: Neurochemical and electrophysiological deficits in the ventral hippocampus and selective behavioral alterations caused by high-fat diet in female C57BL/6 mice. Neuroscience. 2015;297:170-181.

[10] Kyseľová Z., Sotníková R., Navarová J., Gajdošík A., Paulovičová E., Bernátová I., Bezek Š.: The effect of SMe1EC2 and fenofibrate on selected parameters in hereditary hypertriglyceridemic rats fed high-cholesterol diet. Presented at: International Symposium. Nitric Oxide: From Basic Regulation to Lifestylerelated Diseases; September 16-21, 2009; Tučepi, Croatia.

[11] Launer L. J., Masaki K., Petrovitch H., Foley D., Havlik R. J.: The association between midlife blood pressure levels and latelife cognitive function. JAMA. 1995;274:1846–1851.

[12] Liu Z., Patil I. Y., Jiang T., Sancheti H., Walsh J. P., Stiles B. L., Yin F., Cadenas E.: High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity. Am J Pathol. 2009;175: 355-364.

[13] Meyer-Sabellek W., Brasch H.: Atherosclerosis, inflammation, leukocyte function and the effect of statins. J Hypertens, 2006;24:2349-2351.

[14] O’Neil S, O’Driscoll L.: Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obesity Reviews, 2015;16:1-12.

[15] de Sousa Rodrigues M. E., Bekhbat M., Houser M. C., Chang J., Walker D. I., Jones D. P., Oller do Nascimento C. M. P., Barnum Ch. J., Tansey M. G.: Chronic psychological stress and high-fat high fructose diet disrupt metabolic and inflammatory gene networks in the brain, liver, and gut and promote behavioral deficits in mice. Brain Behav Immun. 2017;59:158-172

[16] Štolba P., Dobešová Z., Hušek P., Opltová H., Zicha J., Vrána A., Kuneš J.: The hypertriglyceridemic rat as a genetic model of hypertension and diabetes. Life Sci. 1992;51:733-740.

[17] Treviño S., Vázquez-Roque R. A., López-López G., Perez-Cruz C., Moran C., Handal-Silva A., González-Vergara E., Guevara J., Díaz A.: Metabolic syndrome causes recognition memory impairments and reduced the hippocampal neuronal plasticity in rats. J Chem Neuroanat. 2017; 82:65-75.

[18] Valladolid-Acebes I., Merino B., Principato A., Fole A., Barbas C., Lorenzo M. P., Garcia A., Del Olmo N., Ruiz-Gayo M., Cano V.: High-fat diets induce changes in hippocampal glutamate metabolism and neurotransmission. Am J Physiol Endocrinol Metab. 2013;302:396-402.

[19] Qiu C., Winblad B., Fratiglioni L.: The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol. 2005;4:8487–8499.

[20] Yates K. F., Sweat V., Yau P. L., Turchiano M. M., Convit A.: Impact of metabolic syndrome on cognition and Brain. Arterioscler Thromb Vasc Biol. 2012;32:2060-2067.

[21] Yau P. L., Castro M. G., Tagani A., Tsui W.H., Convit A.: Obesity and metabolic syndrome and structural brain impairments in adolescence. Pediatrics, 2012;130: 856-864.

European Pharmaceutical Journal

Acta Facultatis Pharmaceuticae Universitatis Comenianae (formerly)

Journal Information

CiteScore 2017: 0.24

SCImago Journal Rank (SJR) 2017: 0.129
Source Normalized Impact per Paper (SNIP) 2017: 0.140


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 90 90 41
PDF Downloads 66 66 26