Development of a novel model of cholecystectomy in subsequently ovariectomized mice and characterization of metabolic and gastrointestinal phenotypes: a pilot study
Autor: | Tzu Wen L. Cross, Kelly S. Swanson, Miranda D. Vieson, Erik R. Nelson, Lindsey Ly, Celeste Alexander, Jason M. Ridlon, Anne H Lee |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.drug_class Population Physiology Blood lipids Pilot Projects Cholesterol 7 alpha-hydroxylase 03 medical and health sciences Mice 0302 clinical medicine Internal medicine medicine Animals Humans Cholecystectomy Gallbladder removal lcsh:RC799-869 education Feces Triglycerides education.field_of_study business.industry Gastroenterology General Medicine Hepatology medicine.disease Menopause Mice Inbred C57BL 030104 developmental biology Phenotype Metabolism Estrogen Ovariectomized rat lcsh:Diseases of the digestive system. Gastroenterology 030211 gastroenterology & hepatology Female Microbiome business Research Article |
Zdroj: | BMC Gastroenterology BMC Gastroenterology, Vol 21, Iss 1, Pp 1-14 (2021) |
ISSN: | 1471-230X |
Popis: | 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. |
Databáze: | OpenAIRE |
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