doi: 10.1111/j.1463-1326.2009.01092.x ORIGINAL ARTICLE Dietary supplementation of tetradecylthioacetic acid increases feed intake but reduces body weight gain and adipose depot sizes in rats fed on high-fat diets A. J. Wensaas, 1 A. C. Rustan, 2 M. H. Rokling-Andersen, 1 R. Caesar, 1 J. Jensen, 3 O. Kaalhus, 4 B. A. Graff, 5 O. A. Gudbrandsen, 6 R. K. Berge, 6,7 and C. A. Drevon 1 1 Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway 2 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo Norway 3 National Institute of Occupational Health, Oslo, Norway 4 Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway 5 Norwegian Knowledge Center for the Health Services, Oslo, Norway 6 Lipid Research Group, Institute of Medicine, University of Bergen, Norway 7 Department of Heart Diseases, Haukeland University Hospital, Bergen, Norway Aim:The pan-peroxisome proliferator-activated receptor (PPAR) ligand and fatty acid analogue tetradecylthioacetic acid (TTA) may reduce plasma lipids and enhance hepatic lipid metabolism, as well as reduce adipose tissue sizes in rats fed on high-fat diets. This study further explores the effects of TTA on weight gain, feed intake and adipose tissue functions in rats that are fed a high-fat diet for 7 weeks. Methods: The effects on feed intake and body weight during 7 weeks’ dietary supplement with TTA (∼200 mg/kg bw) were studied in male Wistar rats fed on a lard-based diet containing ∼40% energy from fat. Adipose tissue mass, body composition and expression of relevant genes in fat depots and liver were measured at the end of the feeding. Results: Despite higher feed intake during the final 2 weeks of the study, rats fed on TTA gained less body weight than lard-fed rats and had markedly decreased subcutaneous, epididymal, perirenal and mesenteric adipose depots. The effects of TTA feeding with reduced body weight gain and energy efficiency (weight gain/feed intake) started between day 10 and 13. Body contents of fat, protein and water were reduced after feeding lard plus TTA, with a stronger decrease in fat relative to protein. Plasma lipids, including Non-Esterified Fatty Acids (NEFA), were significantly reduced, whereas fatty acid β-oxidation in liver and heart was enhanced in lard plus TTA-fed rats. Hepatic UCP3 was expressed ectopically both at protein and mRNA level (>1900-fold), whereas Ucp1 mRNA was increased ∼30-fold in epididymal and ∼90-fold in mesenteric fat after lard plus TTA feeding. Conclusion: Our data support the hypothesis that TTA feeding may increase hepatic fatty acid β-oxidation, and thereby reduce the size of adipose tissues. The functional importance of ectopic hepatic UCP3 is unknown, but might be associated with enhanced energy expenditure and thus the reduced feed efficiency. Keywords: adipose tissue, body weight, energy expenditure, feed intake, pan-PPAR agonist, tetradecylthioacetic acid Received 3 November 2008; returned for revision 28 February 2009; revised version accepted 31 May 2009 Correspondence: Christian A. Drevon, Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P. O. Box 1046, Blindern, 0316 Oslo, Norway. E-mail: c.a.drevon@medisin.uio.no 1034 Diabetes, Obesity and Metabolism, 11, 2009, 1034–1049 © 2009 Blackwell Publishing Ltd