Development of a novel model of cholecystectomy in subsequently ovariectomized mice and characterization of metabolic and gastrointestinal phenotypes: a pilot study.

Affiliation

Alexander C(1), Cross TL(2), Lee AH(3), Ly LK(2), Vieson MD(4), Ridlon JM(2)(3)(5)(6), Nelson ER(2)(5)(6)(7)(8), Swanson KS(9)(10).
Author information:
(1)Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1207 W Gregory Dr, Urbana, IL, 61801, USA. [Email]
(2)Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1207 W Gregory Dr, Urbana, IL, 61801, USA.
(3)Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
(4)College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
(5)Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
(6)Carl R. Woese Institute for Genomic Biology, Anticancer Discovery from Pets to People Theme, University of Illinois Urbana-Champaign, IL, Urbana, USA.
(7)Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
(8)University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL, USA.
(9)Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 1207 W Gregory Dr, Urbana, IL, 61801, USA. [Email]
(10)Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA. [Email]

Abstract

BACKGROUND: Cholecystectomy (XGB) is the most common abdominal surgery performed in the United States and is associated with an increased post-surgery incidence of metabolic and gastrointestinal (GI) diseases. Two main risk factors for XGB are sex (female) and age (40-50 yr), corresponding with onset of menopause. Post-menopausal estrogen loss alone facilitates metabolic dysfunction, but the effects of XGB on metabolic and GI health have yet to be investigated in this population. Study objectives were to (1) identify possible short-term effects of XGB and (2) develop a novel murine model of XGB in human menopause via subsequent ovariectomy (OVX) and assess longitudinal effects of OVX on metabolism, GI physiology, and GI microbiota in XGB mice. METHODS: Female C57BL/6 mice were utilized in two parallel studies (S1&S2). In S1, XGB mice were compared to a non-XGB baseline group after six wk. In S2, mice were XGB at wk0, either sham (SHM) or OVX at wk6, and sacrificed at wk12, wk18, and wk24. Body composition assessment and fresh fecal collections were conducted periodically. Serum and tissues were collected at sacrifice for metabolic and GI health endpoints. RESULTS: Compared to baseline, XGB increased hepatic CYP7A1 and decreased HMGCR relative expression, but did not influence BW, fat mass, or hepatic triglycerides after six wk. In S2, XGB/OVX mice had greater BW and fat mass than XGB/SHM. Cecal microbiota alpha diversity metrics were lower in XGB/OVX mice at wk24 compared the XGB/SHM. No consistent longitudinal patterns in fasting serum lipids, fecal microbial diversity, and GI gene expression were observed between S2 groups. CONCLUSIONS: In addition to developing a novel, clinically-representative model of XGB and subsequent OVX, our results suggest that OVX resulted in the expected phenotype to some extent, but that XGB may modify or mask some responses and requires further investigation.