Lipoic acid prevents high-fat diet–induced dyslipidemia and oxidative stress: A microarray analysis

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Vol. 24; no. 6; pp. 582 - 588
• Main Authors: Yang, Rui-li, M.S, Li, Wu, M.S, Shi, Yong-Hui, M.S, Le, Guo-Wei, Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2008; [New York]: Elsevier Science Inc; Elsevier; Elsevier Limited
• Subjects: Algorithms; Animals; antioxidant activity; Antioxidants; Antioxidants - pharmacology; Biological and medical sciences; blood lipids; Cardiovascular disease; Cholesterol; Cholesterol - biosynthesis; Dehydrogenases; Deoxyribonucleic acid; Diet; diet-related diseases; Dietary Fats - administration & dosage; disease prevention; DNA; DNA microarray; Feeding. Feeding behavior; Free Radical Scavengers; Free radicals; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Gene expression; Gene Expression Profiling; Heat shock proteins; High-fat diet; Homeostasis; human diseases; human nutrition; Hyperlipidemia; Hyperlipidemias - blood; Hyperlipidemias - drug therapy; Ingestion; Laboratory animals; Lipid metabolism; Lipid Metabolism - drug effects; lipid peroxidation; Lipids; Lipids - blood; lipoic acid; Lipoproteins; Liver; low density lipoprotein; Male; Metabolism; Mice; Mice, Inbred C57BL; Microarray Analysis - methods; microarray technology; Oxidation; Oxidation-Reduction; Oxidative stress; Oxidative Stress - drug effects; Peroxidation; Plasma; Polymerase chain reaction; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Software; Thioctic Acid - pharmacology; triacylglycerols; Triglycerides - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; DNA microarray; Oxidative stress; Lipid metabolism; Hyperlipidemia; High-fat diet; Lipoic acid; DNA chip; Metabolic diseases; Lipids; Metabolism; Feeding; Vertebrata; Mammalia; Diet; Fat; Hyperlipemia; Dyslipemia
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2008.02.002

Abstract Objective We previously found that lipoic acid (LA) improved high-fat diet (HFD)–induced dyslipidemia in rats. To elucidate the molecular mechanisms of that effect, we carried out experiments aimed at analyzing biochemical parameters and gene expression profiles. Methods C57BL/6 mice were randomly assigned to one of three groups ( n = 8). The control group consumed an ordinary diet (4.89% fat, w/w). The other two experimental groups were fed with an HFD (21.45% fat, w/w) or an HFD plus 0.1% LA. After 6 wk, plasma lipid level and antioxidant status were examined. To investigate the molecular mechanisms underlying the effects of LA on lipid metabolism and oxidative stress, we examined gene expression profiles in liver using the GeneChip microarray system. The differential expression of genes of interest identified by microarray technique was validated by real-time reverse transcription–polymerase chain reaction. Results HFD resulted in significant alterations in lipid profiles and a depressed antioxidant defense system. LA supplementation induced decreases in lipid peroxidation, plasma cholesterol, triacylglycerols, and low-density lipoprotein cholesterol and an increase in high-density lipoprotein in HFD-fed mice. DNA microarray analysis of the liver showed that LA ingestion upregulated the expression of genes related to β-oxidation and free radical scavenger enzymes, whereas those involved in cholesterol synthesis were downregulated. Conclusion LA can prevent HFD-induced dyslipidemia by modulating lipid metabolism, especially by increasing β-oxidation and decreasing cholesterol synthesis, and oxidative stress by increasing those of free radical scavenger enzyme gene expression.