title: High-calorie diet inflates steatogenic effects of valproic acid in mice.
abstract: Valproic acid (VPA) is an anti-epileptic drug used in patients with convulsive seizures and psychic disorders. Despite its therapeutic use, VPA administration is associated with several side effects of which hepatosteatosis (lipid deposition in liver >10% of organ weight) is of concern. Recently, the consumption of western-type diet rich in fat and simple sugar has increased, the pathological consequences of which has been linked to the escalating incidence of metabolic disorders. The hypothesis of the study is that the metabolic stress induced by high-calorie diet may potentiate VPA-induced hepatosteatosis. Two groups of Swiss Mus musculus male mice weighing 25-35 g were fed either normal chow or high fat and high fructose diet (HFFD) and maintained for 30 days. On the 16th day of the experiment, VPA (100 mg/kg bw) administration was initiated in one set of animals from each group and the other set was left without VPA treatment. Assays were done in the hemolysate, plasma and liver tissue of mice after the experimental period. Deregulated lipid metabolism, loss of insulin sensitivity, enhanced CYP2E1 activity and oxidative damage, and diminution of cellular antioxidants were observed in animals that received HFFD and VPA. HFFD-fed mice are sensitized to VPA toxicity than the normal chow-fed counterparts. The results of this study show that preformed metabolic derangements due to high-energy diet may infuriate VPA-induced hepatosteatosis and insulin resistance.
authors.affiliation: a Department of Biochemistry and Biotechnology , Annamalai University , Annamalai Nagar , Tamil Nadu , India and.
authors.forename: Chandrasekaran
authors.initials: C
authors.lastname: Sathiya Priya
authors.affiliation: b Department of Pathology , Mahatma Gandhi Medical College and Research Institute , Puducherry , India.
authors.forename: Krishnamoorthy
authors.initials: K
authors.lastname: Bhavani
authors.affiliation: a Department of Biochemistry and Biotechnology , Annamalai University , Annamalai Nagar , Tamil Nadu , India and.
authors.forename: Carani Venkatraman
authors.initials: CV
authors.lastname: Anuradha
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D066273:Diet, Western / Q000009:adverse effects*; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000009:adverse effects; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D005234:Fatty Liver / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D014635:Valproic Acid / Q000097:blood / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007328:Insulin; D008055:Lipids; D014635:Valproic Acid
keywords: Hepatosteatosis; high fat and high fructose diet; lipid metabolism; oxidative stress; valproic acid