Effect of Orlistat on Fecal Fat, Fecal Biliary Acids, and Colonic Cell Proliferation in Obese Subjects

Dennis J. Ahnen, Roberto Guerciolini, Jonathan Hauptman, Steven Blotner, Cindy J. Woods, Michael J. Wargovich

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background & Aims: Orlistat is a weight management agent that selectively inhibits gastrointestinal lipase activity. Because of orlistat's mode of action, increased fecal fat is presented to the colonic mucosa, and fecal bile acid and free fatty acid composition may be altered during treatment. Our aim was to assess the effect of treatment of obese subjects with orlistat 120 mg 3 times a day for 6 weeks on fecal lipid and bile acid parameters and colonic mucosal cell proliferation. Methods: Twenty-four obese (body mass index, 30-40 kg/m2) but otherwise healthy male and female subjects were enrolled in a single-center, randomized, double-blind, placebo-controlled, parallel-group study. Participants were hospitalized during days 1-3 and 33-42 of treatment and were treated as outpatients for the remaining days. Results: Treatment with orlistat for 6 weeks resulted in significantly greater increases in fecal weight, total fecal fat, and fecal free fatty acids than placebo. Total fecal bile acid amounts decreased slightly with orlistat, and increased significantly with placebo treatment (P < .05 between-group difference). Orlistat did not alter colonic cell proliferation as assessed by the 3 proliferative indices (5-bromo-2-deoxyuridine, whole crypt mitotic count, and proliferating cell nuclear antigen). Conclusions: Biochemical changes in fecal composition related to the pharmacodynamic mode of action of orlistat are not accompanied by altered colonic cell proliferation, a putative biomarker of colon cancer risk.

Original languageEnglish (US)
Pages (from-to)1291-1299
Number of pages9
JournalClinical Gastroenterology and Hepatology
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Fingerprint Dive into the research topics of 'Effect of Orlistat on Fecal Fat, Fecal Biliary Acids, and Colonic Cell Proliferation in Obese Subjects'. Together they form a unique fingerprint.

Cite this