Can Exercise Ameliorate Memory Impairment via PPAR Gamma Activation in Rats Fed A High-Fat Diet?

Abstract views: 105 / PDF downloads: 37




Experimental obesity model, exercise, learning–memory, PPAR gamma


Objective: This study aimed at determining the molecular effects of exercise on obesity treatment and cognitive impairment by examining the relationship between exercise (one of the non-pharmacological approaches) and PPAR-γ.
Methods: We classified 32 rats into four experimental groups: random control (C), obese (Ob), control exercise group (C+Ex), and obese exercise (Ob+Ex). The experimental groups were fed with a high-fat diet (45% fat) and standard rodent chow. The exercise program commenced after obesity diagnosis (30 min/day) and continued until the end of the study. At the end of the study, all rats underwent a learning–memory test in a Morris water tank, and the hippocampus of all rats were removed under anesthesia to study the PPAR gamma gene expression level.
Results: The escape latency was significantly different between the exercise groups and non-exercise groups (p<0.05). Molecular analysis revealed an increase in PPAR-γ gene expression levels in the exercise groups compared with that observed in the non-exercise groups, but no significant difference was found when comparing the gene expression levels between the groups (p>0.05).
Conclusion: PPAR-γ gene expression levels were upregulated in the exercise groups. In addition, the exercise groups performed better with regards to cognitive functions. This result provides a clue about the impact of exercise on the molecular pathway with respect to performance differences in cognitive function due to obesity.


Metrics Loading ...


Hruby A, Hu FB. The Epidemiology of Obesity: A Big Picture. Pharmacoeconomics 2015; 33: 673-89.

Obesity and Overweight [Internet]. Who. 2018 [cited 2018 Jan 24]. Available from:

Singh RK, Kumar P, Mahalingam K. Molecular genetics of human obesity: A comprehensive review. C R Biol 2017; 340: 87-108.

Nguyen JCD, Killcross AS, Jenkins TA. Obesity and cognitive decline : role of inflammation and vascular changes. Front Neurosci 2014; 8: 375.

Bradley RL, Jeon JY, Liu F, Maratos-flier E. Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice. Am J Physiol Endocrinol Metab 2008; 295: 586-94.

Asl NA, Sheikhzade F, Torchi M, Roshangar L, Khamnei S. Long-term regular exercise memory and learning in young but not in older rats. Pathophysiology 2008; 15: 9-12.

Mandolesi L, Polverino A, Montuori S, Foti F, Ferraioli G, Sorrentino P, et al. Effects of physical exercise on cognitive functioning and wellbeing: Biological and psychological benefits. Front Psychol 2018; 9: 509.

Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Tech Res 2011; 2: 236-40.

Heming M, Gran S, Jauch S-L, Fischer-Riepe L, Russo A, Klotz L, et al. Peroxisome Proliferator-Activated Receptor- γ Modulates the Response of Macrophages to Lipopolysaccharide and Glucocorticoids. Front Immunol 2018; 9: 893.

Thiruchelvam K, Nanayakkara G, Parameshwaran K, Bagasrawala I, Ahuja M, Abdelrahman E. Central activation of PPAR-gamma ameliorates diabetes induced cognitive dysfunction and improves BDNF expression. Neurobiol Aging 2015; 36: 1451-61.

Marques C, Meireles M, Norberto S, Leite J, Freitas J, Pestana D, et al. High-fat diet-induced obesity Rat model: a comparison between Wistar and Sprague-Dawley Rat. Adipocyte 2015; 5: 11-21.

Lu Y, Li H, Shen S, Shen Z, Xu M, Yang C, et al. Swimming exercise increases serum irisin level and reduces body fat mass in high- fat-diet fed Wistar rats. Lipids Heal Dis 2016; 15: 93.

Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 2006; 1: 848-58.

Song MK, Kim EJ, Kim JK, Park HK, Lee SG. Effect of regular swimming exercise to duration-intensity on neurocognitive function in cerebral infarction rat model. Neurol Res 2019; 41: 37-44.

Cassel JC, Cassel S, Galani R, Kelche C, Will B, Jarrad L. Fimbria-fornix vs selective hippocampal lesions in rats: effects on locomotor activity and spatial learning and memory. Neurobiol Learn Mem 1998; 69: 22-45.

Lutz TA, Woods SC. Overview of Animal Models of Obesity. Curr Protoc Pharmacol 2012; Unit 5; 61.

Arnoldussen IA, Kiliaan AJ, Gustafson DR. Obesity and dementia: Adipokines interact with the brain. Eur Neuropsychopharmacol 2014; 24: 1982-99.

Pratchayasakul W, Sa-nguanmoo P, Sivasinprasasn S, Pintana H, Tawinvisan R, Sripetchwandee J, et al. Obesity accelerates cognitive decline by aggravating mitochondrial dysfunction, insulin resistance and synaptic dysfunction under estrogen-deprived conditions. Horm Behav 2015; 72: 68-77.

Sa-nguanmoo P, Tanajak P, Kerdphoo S, Satjaritanun P, Wang X, Liang G, et al. FGF21 improves cognition by restored synaptic plasticity, dendritic spine density, brain mitochondrial function and cell apoptosis in obese-insulin resistant male rats. Horm Behav 2016; 85: 86-95.

Ravizza T, Rizzi M, Perego C, Richichi C, Vel J, Mosh SL, et al. Inflammatory Response and Glia Activation in Developing Rat Hippocampus after Status Epilepticus. Epilepsia 2005; 46: 113-7.

Petridou A, Siopi A, Mougios V. Exercise in the management of obesity. Metabolism 2019; 92: 163-9.

Fleury G, Speretta F, Rosante IMC, Duarte FO, Richard Leite D, de Souza Lino AD, et al. The effects of exercise modalities on adiposity in obese rats. Clinics (Sao Paulo) 2012; 67: 1469-77.

Phillips C, Baktir MA, Srivatsan M, Salehi A. Neuroprotective effects of physical activity on the brain: A closer look at trophic factor signaling. Front Cell Neurosci 2014; 8: 170.

Saraulli D, Costanzi M, Mastrorilli V, Farioli-vecchioli S. The Long Run: Neurogenesis from Youth to Old Age. Curr Neuropharmacol 2017; 15: 519-33.

Farmer J, Zhao X, van Praag H, Wodtke K, Gage FH, Christie BR. Effects of Voluntary Exercise on Synaptic Plastıcity and Gene Expression in the Dentate Gyrus of Adult Male Sprague - Dawley Rats In Vıvo. Neuroscience 2004; 124: 71-9.

Erickson KI, Raji CA, Lopez OL, Becker JT, Rosano C, Newman AB, et al. Physical activity predicts gray matter volume in late adulthood The Cardiovascular Health Study. Neurology 2010; 75: 1415-22.

Lee JM, Park JM, Song MK, Kim YJ, Kim YJ. Comparison of the behavioral effects of exercise and high fat diet on cognitive function in adolescent rats. J Exerc Rehabil 2016; 12: 520-5.

Woo J, Shin KO, Park SY, Jang KS, Kang S. Effects of exercise and diet change on cognition function and synaptic plasticity in high fat diet induced obese rats. Lipids Health Dis 2013; 12: 144.

Marion-letellier R, Savoye G, Ghosh S. Fatty acids , eicosanoids and PPAR gamma. Eur J Pharmacol 2016; 785: 44-9.

Hajjar T, Meng GY, Rajion MA, Vidyadaran S, Othman F, Farjam AS. Omega 3 polyunsaturated fatty acid improves spatial learning and hippocampal Peroxisome Proliferator Activated Receptors ( PPAR α and PPAR γ ) gene expression in rats. BMC Neurosci 2012; 18: 109.

Zhou L, Chen T, Li G, Wu C, Wang C, Li L. et al. Activation of PPAR γ Ameliorates Spatial Cognitive Deficits through Restoring Expression of AMPA Receptors in Seipin Knock-Out Mice. J Neurosci 2016; 27: 36: 1242-53.

Gao F, Zang DY, Li YJ, Zhang Q, Wang HB, Mu YM et al. Pioglitazone Improves the Ability of Learning and Memory via Activating ERK1/2 Signaling Pathway in the Hippocampus of T2DM Rats. Neurosci Lett 2017: 651; 165-70.

Govindarajulu M, Pinky PD, Bloemer J, Suppiramaniam V, Amin R, Ghanei N. Signaling Mechanisms of Selective PPAR γ Modulators in Alzheimer ‘ s Disease. PPAR Res 2018; 2018: 2010675.

Xu B. BDNF ( I ) rising from Exercise. Cell Metab 2013; 5: 612-4.




How to Cite

Yılmaz, İbrahim, Demirel, C., Balcı, S. O., & Akarsu, E. (2020). Can Exercise Ameliorate Memory Impairment via PPAR Gamma Activation in Rats Fed A High-Fat Diet?. European Journal of Therapeutics, 26(4), 275–281.



Original Articles