Grape seed and skin extract prevents high-fat diet-induced brain lipotoxicity in rat.
Obesity is related to an elevated risk of dementia and the physiologic mechanisms whereby fat adversely affects the brain are poorly understood. The present investigation analyzed the effect of a high fat diet (HFD) on brain steatosis and oxidative stress and the intracellular mediators involved in signal transduction, as well as the protection offered by grape seed and skin extract (GSSE). HFD induced ectopic deposition of cholesterol and phospholipid but not triglyceride. Moreover brain lipotoxicity is linked to an oxidative stress characterized by increased lipoperoxidation and carbonylation, inhibition of glutathione peroxidase and superoxide dismutase activities, depletion of manganese and a concomitant increase in ionizable calcium and acetylcholinesterase activity. Importantly GSSE alleviated all the deleterious effects of HFD treatment. Altogether our data indicated that HFD could find some potential application in the treatment of manganism and that GSSE should be used as a safe anti-lipotoxic agent in the prevention and treatment of fat-induced brain injury.
Laboratoire des Substances Bioactives, Centre de Biotechnologie de Borj Cedria, BP-901, 2050 Hammam-Lif, Tunisia.
Kamel
K
Charradi
Salem
S
Elkahoui
Ines
I
Karkouch
Ferid
F
Limam
Fethy Ben
FB
Hassine
Ezzedine
E
Aouani
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D001927:Brain Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D004041:Dietary Fats / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D056604:Grape Seed Extract / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008345:Manganese / Q000378:metabolism; D013058:Mass Spectrometry; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D027843:Vitis / Q000737:chemistry*
D000975:Antioxidants; D004041:Dietary Fats; D056604:Grape Seed Extract; D008345:Manganese; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase; D005978:Glutathione; D002118:Calcium