title: Bile acid binding resin improves metabolic control through the induction of energy expenditure.
abstract: BACKGROUND
  Besides well-established roles of bile acids (BA) in dietary lipid absorption and cholesterol homeostasis, it has recently become clear that BA is also a biological signaling molecule. We have shown that strategies aimed at activating TGR5 by increasing the BA pool size with BA administration may constitute a significant therapeutic advance to combat the metabolic syndrome and suggest that such strategies are worth testing in a clinical setting. Bile acid binding resin (BABR) is known not only to reduce serum cholesterol levels but also to improve glucose tolerance and insulin resistance in animal models and humans. However, the mechanisms by which BABR affects glucose homeostasis have not been established. We investigated how BABR affects glycemic control in diet-induced obesity models.
  
  
  RESULTS
  We evaluated the metabolic effect of BABR by administrating colestimide to animal models for the metabolic syndrome. Administration of BABR increased energy expenditure, translating into significant weight reduction and insulin sensitization. The metabolic effects of BABR coincide with activation of cholesterol and BA synthesis in liver and thermogenesis in brown adipose tissue. Interestingly, these effects of BABR occur despite normal food intake and triglyceride absorption. Administration of BABR and BA had similar effects on BA composition and thermogenesis, suggesting that they both are mediated via TGR5 activation.
  
  
  CONCLUSIONS
  Our data hence suggest that BABR could be useful for the management of the impaired glucose tolerance of the metabolic syndrome, since they not only lower cholesterol levels, but also reduce obesity and improve insulin resistance.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. wmitsu@sc.itc.keio.ac.jp
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kohkichi
authors.initials: K
authors.lastname: Morimoto
authors.forename: Sander M
authors.initials: SM
authors.lastname: Houten
authors.forename: Nao
authors.initials: N
authors.lastname: Kaneko-Iwasaki
authors.forename: Taichi
authors.initials: T
authors.lastname: Sugizaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Horai
authors.forename: Chikage
authors.initials: C
authors.lastname: Mataki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sato
authors.forename: Karin
authors.initials: K
authors.lastname: Murahashi
authors.forename: Eri
authors.initials: E
authors.lastname: Arita
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000737:chemistry*; D004734:Energy Metabolism; D004811:Epichlorohydrin / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007093:Imidazoles / Q000737:chemistry*; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012117:Resins, Synthetic / Q000737:chemistry*; D015398:Signal Transduction
chemical_list: D001647:Bile Acids and Salts; C513561:Gpbar1 protein, mouse; D007093:Imidazoles; D043562:Receptors, G-Protein-Coupled; D012117:Resins, Synthetic; C417427:colestimide; D004811:Epichlorohydrin; D002792:Cholestyramine Resin; D002784:Cholesterol; D005947:Glucose