Bile Acid Binding Resin Improves Metabolic Control through the Induction of Energy Expenditure

Mitsuhiro Watanabe, Kohkichi Morimoto, Sander M. Houten, Nao Kaneko-Iwasaki, Taichi Sugizaki, Yasushi Horai, Chikage Mataki, Hiroyuki Sato, Karin Murahashi, Eri Arita, Kristina Schoonjans, Tatsuya Suzuki, Hiroshi Itoh, Johan Auwerx

Research output: Contribution to journalArticle

65 Citations (Scopus)

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. Methods and Findings: 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. Conclusion: 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.

Original languageEnglish
Article numbere38286
JournalPLoS One
Volume7
Issue number8
DOIs
Publication statusPublished - 2012 Aug 29

Fingerprint

bile acids
Bile Acids and Salts
energy expenditure
Energy Metabolism
resins
Resins
metabolic syndrome
Cholesterol
cholesterol
Thermogenesis
glucose tolerance
Insulin
heat production
Glucose
insulin resistance
Insulin Resistance
homeostasis
Animals
obesity
Homeostasis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Watanabe, M., Morimoto, K., Houten, S. M., Kaneko-Iwasaki, N., Sugizaki, T., Horai, Y., ... Auwerx, J. (2012). Bile Acid Binding Resin Improves Metabolic Control through the Induction of Energy Expenditure. PLoS One, 7(8), [e38286]. https://doi.org/10.1371/journal.pone.0038286

Bile Acid Binding Resin Improves Metabolic Control through the Induction of Energy Expenditure. / Watanabe, Mitsuhiro; Morimoto, Kohkichi; Houten, Sander M.; Kaneko-Iwasaki, Nao; Sugizaki, Taichi; Horai, Yasushi; Mataki, Chikage; Sato, Hiroyuki; Murahashi, Karin; Arita, Eri; Schoonjans, Kristina; Suzuki, Tatsuya; Itoh, Hiroshi; Auwerx, Johan.

In: PLoS One, Vol. 7, No. 8, e38286, 29.08.2012.

Research output: Contribution to journalArticle

Watanabe, M, Morimoto, K, Houten, SM, Kaneko-Iwasaki, N, Sugizaki, T, Horai, Y, Mataki, C, Sato, H, Murahashi, K, Arita, E, Schoonjans, K, Suzuki, T, Itoh, H & Auwerx, J 2012, 'Bile Acid Binding Resin Improves Metabolic Control through the Induction of Energy Expenditure', PLoS One, vol. 7, no. 8, e38286. https://doi.org/10.1371/journal.pone.0038286
Watanabe, Mitsuhiro ; Morimoto, Kohkichi ; Houten, Sander M. ; Kaneko-Iwasaki, Nao ; Sugizaki, Taichi ; Horai, Yasushi ; Mataki, Chikage ; Sato, Hiroyuki ; Murahashi, Karin ; Arita, Eri ; Schoonjans, Kristina ; Suzuki, Tatsuya ; Itoh, Hiroshi ; Auwerx, Johan. / Bile Acid Binding Resin Improves Metabolic Control through the Induction of Energy Expenditure. In: PLoS One. 2012 ; Vol. 7, No. 8.
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