TitleLipoic acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretion.
Publication TypeJournal Article
Year of Publication2009
AuthorsButler JA, Hagen TM, Moreau R
JournalArch Biochem Biophys
Date Published2009 May 01
KeywordsAMP-Activated Protein Kinases, Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Energy Intake, Fatty Acids, Glycogen, Hypertriglyceridemia, Lipoproteins, VLDL, Liver, Male, Oxidation-Reduction, PPAR alpha, Rats, Rats, Zucker, Thioctic Acid, Triglycerides

Elevated blood triacylglycerol (TG) is a significant contributing factor to the current epidemic of obesity-related health disorders, including type-2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. The observation that mice lacking the enzyme sn-glycerol-3-phosphate acyltransferase are protected from insulin resistance suggests the possibility that the regulation of TG synthesis be a target for therapy. Five-week-old Zucker Diabetic Fatty (ZDF) rats were fed a diet containing (R)-alpha-lipoic acid (LA, approximately 200mg/kg body weight per day) for 5 weeks. LA offset the rise in blood and liver TG by inhibiting liver lipogenic gene expression (e.g. sn-glycerol-3-phosphate acyltransferase-1 and diacylglycerol O-acyltransferase-2), lowering hepatic TG secretion, and stimulating clearance of TG-rich lipoproteins. LA-induced TG lowering was not due to the anorectic properties of LA, as pair-fed rats developed hypertriglyceridemia. Livers from LA-treated rats exhibited elevated glycogen content, suggesting dietary carbohydrates were stored as glycogen rather than becoming lipogenic substrate. Although AMP-activated protein kinase (AMPK) reportedly mediates the metabolic effects of LA in rodents, no change in AMPK activity was observed, suggesting LA acted independently of this kinase. The hepatic expression of peroxisome proliferator activated receptor alpha (PPARalpha) target genes involved in fatty acid beta-oxidation was either unchanged or decreased with LA, indicating a different mode of action than for fibrate drugs. Given its strong safety record, LA may have potential clinical applications for the treatment or prevention of hypertriglyceridemia and diabetic dyslipidemia.

Alternate JournalArch. Biochem. Biophys.
PubMed ID19232511
PubMed Central IDPMC2771166
Grant ListP01 AT 002034 / AT / NCCIH NIH HHS / United States
R01 AG017141 / AG / NIA NIH HHS / United States
2R01 AG 017141 / AG / NIA NIH HHS / United States
P01 AT002034-010002 / AT / NCCIH NIH HHS / United States
R01 AG017141-01A1 / AG / NIA NIH HHS / United States
P01 AT002034 / AT / NCCIH NIH HHS / United States