Weight gain in mice on a high caloric diet and chronically treated with omeprazole depends on sex and genetic background

Abstract

The impact of omeprazole (OM), a widely used over-the-counter proton pump inhibitor, on weight gain has not been extensively explored. We examined what factors, e.g., diet composition, microbiota, genetic strain, and sex, might affect weight gain in mice fed a high caloric diet while on OM. Inbred C57BL/6J strain, a 50:50 hybrid (B6SJLF1/J) strain, and mice on a highly mixed genetic background were fed four diets: standard chow (STD, 6% fat), STD with 200 ppm OM (STD + O), a high-energy chow (HiE, 11% fat), and HiE chow with OM (HiE + O) for 17 wk. Metabolic analysis, body composition, and fecal microbiota composition were analyzed in C57BL/6J mice. Oral glucose tolerance tests were performed using mice on the mixed background. After 8 wk, female and male C57BL/6J mice on the HiE diets ate less, whereas males on the HiE diets compared with the STD diets gained weight. All diet treatments reduced energy expenditure in females but in males only those on the HiE + O diet. Gut microbiota composition differed in the C57BL/6J females but not the males. Hybrid B6SJLF1/J mice showed similar weight gain on all test diets. In contrast, mixed strain male mice fed a HiE + O diet gained ∼40% more weight than females on the same diet. In addition to increased weight gain, mixed genetic mice on the HiE + O diet cleared glucose normally but secreted more insulin. We concluded that sex and genetic background define weight gain and metabolic responses of mice on high caloric diets and OM.

Core 1–derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer

“…For long-term studies, WT and GEC C1galt1 −/− mice (∼2 mo, littermate pairs) mice were given 0.02% wt/wt OME in a base diet identical to control mice (TestDiet 5WRM, #1818774–203; Saqui-Salces et al, 2017) and i.p. injection of OME (#73590-58-6; Cayman Chemical) in dimethylformamide at a concentration of 20 mg/ml diluted 1:9 with sterile PBS (final concentration, 2 mg/ml, 20 mg/kg for injection).…”

Alterations in gut microbiota and bile acids by proton‐pump inhibitor use and possible mediating effects on elevated glucose levels and insulin resistance

“…The mechanism underlying the association between PPI use and metabolic disorders has yet to be identified, but accumulating evidence suggested that the gut microbiota‐bile acids (BAs) axis may mediate this association. Experimental and human studies have demonstrated that PPIs can influence gut microbiota by suppressing acid production and increasing gastric pH 16,17 . On a population level, PPIs have a bigger impact on the gut microbiome than antibiotics 16 .…”

“…Experimental and human studies have demonstrated that PPIs can influence gut microbiota by suppressing acid production and increasing gastric pH. 16,17 On a population level, PPIs have a bigger impact on the gut microbiome than antibiotics. 16 A recent systematic review indicated that diabetic subjects had a decrease in abundance of Faecalibacterium, Roseburia, Bacteroides vulgatus, and several Bifidobacterium spp., and an increase in the abundance of Fusobacterium and Ruminococcus, 18 suggesting a vital role of gut microbiota in metabolic health and diseases.…”

Evidence for proton-pump inhibitor (PPI)-associated dysbiosis in metabolically unhealthy obesity

“…, lean vs. fat mass), metabolism ( i.e. , food intake, energy expenditure (EE), glucose clearance, glucose-stimulated insulin secretion), and fecal microbiota richness are observed in mice fed a high calorie diet and treated with the PPI omeprazole; results varied depending on sex and genetic background ( 11 ).…”