Resistance to diet-induced obesity conferred by dietary bile acid supplementation in mice is strain specific

K Hüttinger; T Fromme; J Fiamoncini; H Daniel; M Klingenspor

doi:10.1055/s-0032-1330808

Experimental and Clinical Endocrinology & Diabetes, Inhaltsverzeichnis

Resistance to diet-induced obesity conferred by dietary bile acid supplementation in mice is strain specific

K Hüttinger ¹, T Fromme ¹, J Fiamoncini ², H Daniel ¹, M Klingenspor ¹

¹Molecular Nutritional Medicine, 3Nutritional Physiology Technische Universität München, Else Kröner-Fresenius Zentrum, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan
²University of Sao Paulo, Institute of Biomedical Sciences, Department of Physiology and Biophysics

Abstract

Bile acids (BA) may function as signaling molecules in a number of peripheral target tissues. It has already been shown that BA confer resistance to diet-induced obesity (DIO) in brown adipose tissue of C57BL/6J (B6) mice by inducing thermogenesis. In our study, we aimed to assess the relevance of brown adipocytes within white adipose tissue depots in this context.

B6 and 129Sv/Ev mice were assigned to one of four different diet groups: low fat (LFD) or high fat (HFD) diet either with or without cholic acid supplementation. Energy assimilation, body mass development as well as body composition were determined. Inguinal white adipose tissue (iWAT) was screened for brite adipocyte recruitment by preparing histological sections as well as conducting quantitative PCR measurements of brown adipocyte markers. Moreover, plasma BA concentration was measured by HPLC-MS/MS.

Both mouse strains displayed HFD-induced obesity. Cholic acid supplementation of LFD did not alter the body mass trajectory. As expected, feeding the HFD supplemented with cholic acid protected B6 mice from DIO. Surprisingly, cholic acid supplementation did not attenuate DIO in HFD fed 129Sv/Ev mice. Since energy assimilation was not affected by dietary BA, cholic acid must exert its protective effect in B6 mice by increasing energy expenditure.

This suggestion was underlined by iWAT analyses: Cholic acid supplementation caused brite adipocyte recruitment exclusively in HFD fed B6 mice, indicated by the morphological appearance of multilocular cells as well as increased brown adipocyte marker expression levels.

Moreover, plasma BA concentration was considerably increased in HFD containing cholic acid fed B6, but not 129Sv/Ev mice.

We identified 129Sv/Ev as a mouse strain resistant to the effects of dietary cholic acid supplementation. In future, this animal model may serve to describe the underlying mechanisms of resistance to diet-induced obesity conferred by bile acids.