pantetheine and Obesity

Scientific evidence continues to accumulate regarding fasting serum triglycerides as an independent risk factor for coronary heart disease. In response, the National Cholesterol Education Program has revised the acceptable level of fasting triglycerides from <200 mg/dL to <150 mg/dL. A significant percentage of Americans suffer from hypertriglyceridemia, and considering the expanding numbers of individuals who are physically inactive, overweight, and suffering from the metabolic syndrome, it is expected that these numbers will continue to rise over the next decade. Fortunately, nutraceutical and lifestyle options have been shown to substantially and consistently reduce this risk factor. This review will focus on management options for the hypertriglyceridemic patient with an emphasis on nicotinic acid, pantethine, fish oils (eicosapentaenoic and docosahexaenoic acids), and modified carbohydrate diets.

Topics: Dietary Carbohydrates; Energy Intake; Evidence-Based Medicine; Exercise; Fasting; Fish Oils; Humans; Hypertriglyceridemia; Metabolic Syndrome; Niacin; Obesity; Pantetheine; Practice Guidelines as Topic; Risk Factors; Risk Reduction Behavior; Severity of Illness Index; Triglycerides; Weight Loss

Hydrolyzed guar gum has gained attention as an anti-obesity agent; however, few studies have focused on its role in amelioration of hepatic-associated metabolic processes. Here, the anti-obesity effect of low molecular weight hydrolyzed guar gum (GMLP, 1-10 kDa) on high-fat diet (HFD)-fed C57BL/6 J mice was investigated via transcriptome and metabolome in liver. GMLP reduced body weight gain and hepatic lipid accumulation dose-dependently, regulated blood lipid levels, and improved liver damage in HFD-fed mice. Integrated transcriptome and metabolome indicated that GMLP mainly altered lipid metabolism pathways (glycerophospholipid metabolism, glycerolipid metabolism, and fatty acid degradation), reduced disease biomarkers of ethyl glucuronide and neopterin, and increased levels of choline, flavin adenine dinucleotide, and pantetheine metabolites. Real-time quantitative PCR showed that GMLP downregulated key genes involved in de novo lipogenesis and triacylglycerol synthesis, while promoting fatty acid oxidation and choline synthesis. This study provides a theoretical basis for GMLP treatment in future clinical applications.

Topics: Animals; Anti-Obesity Agents; Biomarkers; Choline; Diet, High-Fat; Fatty Acids; Flavin-Adenine Dinucleotide; Galactans; Glycerophospholipids; Lipid Metabolism; Lipids; Liver; Mannans; Metabolome; Mice; Mice, Inbred C57BL; Neopterin; Obesity; Pantetheine; Plant Gums; Transcriptome; Triglycerides

Pantethine is a versatile and well-tolerated hypolipidemic agent whose efficacy in this regard appears to be mediated by its catabolic product cystamine, a nucleophile which avidly attacks disulfide groups. An overview of pantethine research suggests that the hypotriglyceridemic activity of pantethine reflects cystamine-mediated inhibition of the hepatic acetyl-CoA carboxylase, which can be expected to activate hepatic fatty acid oxidation. Inhibition of HMG-CoA reductase as well as a more distal enzyme in the cholesterol synthetic pathway may account for pantethine's hypocholesterolemic effects. If pantethine does indeed effectively inhibit hepatic acetyl-CoA carboxylase, it may have adjuvant utility in the hepatothermic therapy of obesity. As a safe and effective compound of natural origin, pantethine merits broader use in the management of hyperlipidemias.

Topics: Acetyl-CoA Carboxylase; Animals; Cholesterol; Cystamine; Fatty Acids; Humans; Hydroxymethylglutaryl CoA Reductases; Hypolipidemic Agents; Liver; Models, Biological; Obesity; Pantetheine; Triglycerides