Abstract
Tetradecylthioacetic acid (TTA) is a synthetic fatty acid with a sulfur substitution in the β-position. This modification renders TTA unable to undergo complete β-oxidation and increases its biological activity, including activation of peroxisome proliferator activated receptors (PPARs) with preference for PPARα. This study investigated the effects of TTA on lipid and lipoprotein metabolism in the intestine and liver of mice fed a high fat diet (HFD). Mice receiving HFD supplemented with 0.75% (w/w) TTA had significantly lower body weights compared to mice fed the diet without TTA. Plasma triacylglycerol (TAG) was reduced 3-fold with TTA treatment, concurrent with increase in liver TAG. Total cholesterol was unchanged in plasma and liver. However, TTA promoted a shift in the plasma lipoprotein fractions with an increase in larger HDL particles. Histological analysis of the small intestine revealed a reduced size of lipid droplets in enterocytes of TTA treated mice, accompanied by increased mRNA expression of fatty acid transporter genes. Expression of the cholesterol efflux pump Abca1 was induced in the small intestine, but not in the liver. Scd1 displayed markedly increased mRNA and protein expression in the intestine of the TTA group. It is concluded that TTA treatment of HFD fed mice leads to increased expression of genes involved in uptake and transport of fatty acids and HDL cholesterol in the small intestine with concomitant changes in the plasma profile of smaller lipoproteins.
Highlights
tetradecylthioacetic acid (TTA) attenuates high fat diet (HFD) induced body weight gain but not HFD induced fatty liver Age matched male C57BL/6J mice were fed HFD as control or HFD supplemented with 0.75% TTA for six weeks
To date only one study have investigated the beneficial effect of TTA in the gut: TTA administration reduced colonic wall thickening and the abundance of inflammatory cytokines in a dextran sodium sulfate induced model of colitis in rats [16]
In the present study we aimed to investigate TTA effects on the intestinal and hepatic lipid and lipoprotein metabolism in mice fed HFD
Summary
The synthetic saturated fatty acid tetradecylthioacetic acid (TTA) is comprised of a 16-carbon backbone with an insertion of a sulfur atom in position 3 (β-position) from its carboxyl end. Tetradecylthioacetic acid promotes redistribution of plasma cholesterol towards large HDL. Swedish Society for Medical Research (https:// www.ssmf.se/) (SSMF;201525) for V.T. Matteo Pedrelli was employed by AstraZeneca from March 2014 to March 2017 within the AstraZenecaMedImmune postdoc programme. Part of the lab costs has been financed by AstraZeneca in form of unrestricted financial support. At the time of the study, Lena Burri was not employed by Aker BioMarine instead she was working as researcher in Rolf Berge’s lab. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
