Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice

• Published in: International Journal of Obesity 2014-08, Vol.38 (8), p.1027-1034
• Main Authors: Teodoro, J S, Zouhar, P, Flachs, P, Bardova, K, Janovska, P, Gomes, A P, Duarte, F V, Varela, A T, Rolo, A P, Palmeira, C M, Kopecký, J
• Format: Article
• Language: English
• Subjects: 631/443/319/2723; 692/699/2743/393; Absorption; Acids; Adipocytes; Adipose tissue; Adipose tissue (brown); Adipose Tissue, Brown - metabolism; Adipose Tissue, White - metabolism; Animal experimentation; Animals; Bile acids; Biological and medical sciences; Biology; Blotting, Western; Body fat; Brown adipose tissue; Carbohydrates; Care and treatment; Chenodeoxycholic acid; Chenodeoxycholic Acid - metabolism; Cholic acid; Corn; Diet; Diet, High-Fat; Dyslipidemia; Energy dissipation; Energy expenditure; Energy Metabolism; Epidemiology; Food; Food intake; Food intolerance; Glucose; Glucose Intolerance - metabolism; Glucose tolerance; Health aspects; Health Promotion and Disease Prevention; High fat diet; Internal Medicine; Ion Channels - metabolism; Lipid Metabolism; Lipid peroxidation; Lipids; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic disorders; Metabolic syndrome X; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Mitochondrial Proteins - metabolism; Non-shivering; Obesity; Obesity - metabolism; Oils & fats; original-article; Oxidation; Oxidative Stress; Phenotypes; Physiological aspects; Physiology; Proteins; Public Health; Real-Time Polymerase Chain Reaction; Reduction; Research design; Reversion; Shivering; Signal Transduction; Thermogenesis; Thyroid gland; Uncoupling Protein 1
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2013.230

Objective: Besides their role in lipid absorption, bile acids (BAs) can act as signalling molecules. Cholic acid was shown to counteract obesity and associated metabolic disorders in high-fat-diet (cHF)-fed mice while enhancing energy expenditure through induction of mitochondrial uncoupling protein 1 (UCP1) and activation of non-shivering thermogenesis in brown adipose tissue (BAT). In this study, the effects of another natural BA, chenodeoxycholic acid (CDCA), on dietary obesity, UCP1 in both interscapular BAT and in white adipose tissue (brite cells in WAT), were characterized in dietary-obese mice. Research design: To induce obesity and associated metabolic disorders, male 2-month-old C57BL/6J mice were fed cHF (35% lipid wt wt −1 , mainly corn oil) for 4 months. Mice were then fed either (i) for 8 weeks with cHF or with cHF with two different doses (0.5%, 1%; wt wt −1 ) of CDCA (8-week reversion); or (ii) for 3 weeks with cHF or with cHF with 1% CDCA, or pair-fed (PF) to match calorie intake of the CDCA mice fed ad libitum ; mice on standard chow diet were also used (3-week reversion). Results: In the 8-week reversion, the CDCA intervention resulted in a dose-dependent reduction of obesity, dyslipidaemia and glucose intolerance, which could be largely explained by a transient decrease in food intake. The 3-week reversion revealed mild CDCA-dependent and food intake-independent induction of UCP1-mediated thermogenesis in interscapular BAT, negligible increase of UCP1 in subcutaneous WAT and a shift from carbohydrate to lipid oxidation. Conclusions: CDCA could reverse obesity in cHF-fed mice, mainly in response to the reduction in food intake, an effect probably occuring but neglected in previous studies using cholic acid. Nevertheless, CDCA-dependent and food intake-independent induction of UCP1 in BAT (but not in WAT) could contribute to the reduction in adiposity and to the stabilization of the lean phenotype.