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.

] Center for Neuroscience and Cell Biology Faculty of Science and Technology University of Coimbra Coimbra Portugal [2] Department of Biology University of Aveiro Aveiro Portugal

] Center for Neuroscience and Cell Biology Faculty of Science and Technology University of Coimbra Coimbra Portugal [2] Department of Life Sciences Faculty of Science and Technology University of Coimbra Coimbra Portugal

Department of Adipose Tissue Biology Institute of Physiology Academy of Sciences of the Czech Republic v v i Prague Czech Republic

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Am J Physiol Regul Integr Comp Physiol. 2012 Sep 1;303(5):R459-76 PubMed

Obesity (Silver Spring). 2009 May;17(5):1023-31 PubMed

FASEB J. 2009 Sep;23(9):3113-20 PubMed

Diabetologia. 2009 May;52(5):941-51 PubMed

MedGenMed. 2003 Oct 15;5(4):8 PubMed

Physiol Rev. 2004 Jan;84(1):277-359 PubMed

Int J Obes. 1985;9(6):443-9 PubMed

Anal Biochem. 1985 Oct;150(1):76-85 PubMed

Curr Diab Rep. 2011 Jun;11(3):160-6 PubMed

Endocrinology. 2005 Mar;146(3):984-91 PubMed

J Cell Sci. 1992 Dec;103 ( Pt 4):931-42 PubMed

Science. 1997 May 16;276(5315):1132-3 PubMed

Biochim Biophys Acta. 2013 May;1831(5):950-9 PubMed

Int J Obes (Lond). 2012 Feb;36(2):262-72 PubMed

J Biol Chem. 2006 Apr 21;281(16):11039-49 PubMed

Diabetes. 2011 Jan;60(1):17-23 PubMed

J Biol Chem. 2005 Aug 19;280(33):29971-9 PubMed

Nature. 2006 Jan 26;439(7075):484-9 PubMed

J Med Chem. 2007 Nov 29;50(24):6048-58 PubMed

Biochim Biophys Acta. 2013 May;1831(5):943-9 PubMed

J Biol Chem. 2011 Jul 29;286(30):26913-20 PubMed

Trends Endocrinol Metab. 2011 Nov;22(11):458-66 PubMed

Cell Metab. 2013 May 7;17(5):798-805 PubMed

PLoS One. 2012;7(8):e38286 PubMed

FEBS Lett. 2011 Feb 4;585(3):539-44 PubMed

Trends Endocrinol Metab. 2011 Apr;22(4):117-23 PubMed

Am J Physiol. 1996 May;270(5 Pt 1):E776-86 PubMed

FEBS Lett. 1984 Feb 13;167(1):10-4 PubMed

Nature. 1979 Sep 6;281(5726):31-5 PubMed

Cell Tissue Res. 1991 Oct;266(1):149-61 PubMed

Mol Endocrinol. 2001 Oct;15(10):1720-8 PubMed

Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E356-67 PubMed

Cell. 2000 Sep 15;102(6):731-44 PubMed

J Biol Chem. 2010 Nov 19;285(47):36759-67 PubMed

J Physiol. 1949 Aug;109(1-2):1-9 PubMed

J Biol Chem. 2010 Mar 5;285(10):7153-64 PubMed

J Lipid Res. 1978 Nov;19(8):1017-24 PubMed

Diabetes. 2010 Feb;59(2):323-9 PubMed

J Clin Invest. 2004 May;113(10):1408-18 PubMed

J Clin Invest. 2011 Jan;121(1):96-105 PubMed

Curr Gastroenterol Rep. 2012 Feb;14(1):55-62 PubMed

Diabetologia. 2011 Oct;54(10):2626-38 PubMed

Genes Dev. 2013 Feb 1;27(3):234-50 PubMed

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