Bile acid binding resins affect diverse molecules to improve metabolic control.

K. Morimoto; M. Watanabe; S. Houten; N. Kaneko-Iwasaki; T. Sugizaki; Y. Horai; C. Mataki; E. Arita; K. Schoonjans; J. Auwerx; H. Itoh

Introduction: Bile acid binding resins (BABRs), anion exchange resins developed as medication for hypercholesterolemia, have been reported to improve glycemic control in patients and animal models with type 2 diabetes mellitus. Although the mechanism has not been clarified yet, we suspect that diverse factors including peripheral bile acid composition and incretins play significant roles in the effect. Besides BABRs, bile acids (BAs) administration has been recently reported to ameliorate metabolic status. In our study, we also administered BAs to metabolic syndrome model mice, to show similarities and differences of BABRs and BAs, to elucidate the mechanism of their anti-metabolic syndrome effects. Methods: We evaluated the metabolic effects of BABR and BA by administering colestimide and cholic acid to male C57BL/6J and KK-Ay mice, at 6 weeks of age, fed normal or high-fat diet supplemented with / without colestimide or cholic acid. A dipeptide peptidase-4 (DPP-4) inhibitor had been also administered alone or combined with colestimide or cholic acid. We performed animal studies including body weight gain, food intake, OGTT, IPGTT, IPITT, serum GLP-1 and insulin concentrations. Morphological study of major tissues, bile acid composition analysis, and gene expression analysis were conducted with samples from the model mice. Results: BABR administration increased energy expenditure to induce weight reduction and insulin sensitization. The effect was similar to that of BA administration on BA composition and thermogenesis. BABR and BA also stimulated GLP-1 secretion, and additional administration of DPP-4 inhibitor augmented antidiabetic effect of BABR and BA. Conclusion: Our data suggest that BABRs could be useful for the management of not only hypercholesterolemia but metabolic syndrome. Futhermore, Combination uses of DPP-4 inhibitor with BABRs or BAs could exhibit great efficacy, providing clues to elucidate the effect of BABRs, and proposing new combination of established medications.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Endocrine Abstracts

P706