Anti-Obesity Effects and Metabolism in DIO Mice of a Novel Hybrid Lipid with Lauric and Lipoic Acid

Abstract

Obesity is a world-wide epidemic and available anti-obesity drugs are associated with side-effects. The effects of oral administration of a novel hybrid lipid obtained by conjugating fatty acid and α-lipoic acid esterified on a glycerol molecule, 1,3-dilauroyl-2-lipoyl-sn-glycerol (diLaLA), on the body weight and food intake of DIO male mice, as well as some other selected metabolic parameters in such mice, was investigated. DIO mice groups on an HFD were fed diLaLA in doses of 10, 50 or 250 mg/kg/day (DIO-10, -50 or -250) for 6 weeks. A fourth group of mice fed with the vehicle (rapeseed oil) alone and served as the control (DIO-V). In comparison with the DIO-V, the highest dose of diLaLA (DIO-250) significantly reduced the body weight, plasma and hepatic Free Fatty Acids (FFAs), as well as the SCD-16 activity index (C16:1n-7/C16:0) in the white adipose tissue of the DIO mice, whereas the liver weight was similar among all the groups. No significant differences were found in the cumulative food intake over the period of 6 weeks among all the groups. Exploratory RT-qPCR analysis indicated that, in the liver, diLaLA induced up-regulation of PPARα, CD 36, CPT1α, Acox, Acca, and AMPK isoforms α1 and γ1, while Acot isoforms 2, 3 and 12 and AMPK isoforms α2 and β1 were down-regulated. The diLaLA reduced the HFD-induced body weight of the mice, possibly through enhancement of the energy expenditure via β-oxidation and suppression of the in vivo lipogenesis, suggesting the potential of diLaLA as a promising candidate against obesity.