Controlling elevated blood
triacylglycerol translates into substantial health benefits. The present study aimed to evaluate the
triacylglycerol-lowering properties of (R)-α-
lipoic acid (LA) once circulating
triacylglycerol levels have become elevated, and identify the molecular targets of LA. Nine-week old male ZDF (fa/fa) rats were fed a chow diet supplemented with 3g LA per kg diet or pair fed for two weeks (8 rats per treatment). We determined changes in blood
triacylglycerol,
insulin, non-
esterified fatty acids, and
ketone bodies concentrations. We analyzed the expression of genes and
proteins involved in
fatty acid and
triacylglycerol metabolism in liver, epididymal fat, and skeletal muscle. Feeding LA to ZDF rats (a) corrected severe
hypertriglyceridemia, (b) lowered abdominal fat mass, (c) raised circulating fibroblast growth factor-21 and
Fgf21 liver gene expression, (d) repressed lipogenic gene expression of
ATP-citrate synthase (Acly),
acetyl-coA carboxylase 1 (Acaca),
fatty acid synthase (Fasn), sn-glycerol-3-phosphate
acyltransferase 1 (Gpam),
adiponutrin (Pnpla3) in the liver and adipose tissue, (e) decreased hepatic
protein levels of ACC1/2, FASN and
5'-AMP-activated protein kinase catalytic subunit α (AMPKα), (f) did not change phospho-AMPKα/AMPKα and phospho-ACC/ACC ratios, (g) stimulated liver gene expression of PPARα target genes
carnitine O-palmitoyltransferase 1β (Cpt1b) and
acyl-CoA thioesterase 1 (Acot1) but not
carnitine O-palmitoyltransferase 1α (Cpt1a). This is evidence that short-term LA feeding to obese rats reverses severe
hypertriglyceridemia.
FGF21 may mediate the beneficial metabolic effects of LA.