Ostα^−/−mice are not protected from western diet-induced weight gain

Abstract

Organic solute transporterα‐OSTβ is a bile acid transporter important for bile acid recycling in the enterohepatic circulation. In comparison to wild‐type mice, Ostα−/− mice have a lower bile acid pool and increased fecal lipids and they are relatively resistant to age‐related weight gain and insulin resistance. These studies tested whether Ostα−/− mice are also protected from weight gain, lipid changes, and insulin resistance which are normally observed with a western‐style diet high in both fat and cholesterol (WD). Wild‐type and Ostα−/− mice were fed a WD, a control defined low‐fat diet (LF) or standard laboratory chow (CH). Surprisingly, although the Ostα−/− mice remained lighter on LF and CH diets, they weighed the same as wild‐type mice after 12 weeks on the WD even though bile acid pool levels remained low and fecal lipid excretion remained elevated. Mice of both genotypes excreted relatively less lipid when switched from CH to LF or WD. WD caused slightly greater changes in expression of genes involved in lipid transport in the small intestines of Ostα−/− mice than wild‐type, but the largest differences were between CH and defined diets. After WD feeding, Ostα−/− mice had lower serum cholesterol and hepatic lipids, but Ostα−/− and wild‐type mice had equivalent levels of muscle lipids and similar responses in glucose and insulin tolerance tests. Taken together, the results show that Ostα−/− mice are able to adapt to a western‐style diet despite low bile acid levels.

Intestinal Farnesoid X Receptor Activation by Pharmacologic Inhibition of the Organic Solute Transporter α-β

“…Furthermore, OSTα-deficient mice, and especially male mice, showed an improved glucose tolerance and insulin sensitivity, 9 albeit less prominently on a high-fat/high-cholesterol diet. 32 In contrast, we observe slightly increased glucose levels in mice receiving the low clofazimine dose. However, this effect was not observed in the high-dose group, suggesting that the effect on glucose levels is not caused by OSTα-OSTβ inhibition itself.…”

Low-dose statin treatment increases prostate cancer aggressiveness

“…Simvastatin was loaded in food pellets and provided ad libitum, thus enabling the uptake of simvastatin in an administration mode and concentration comparable to human subjects, including the activation of the drug in the liver [ 20 ]. We established an experimental design in which we induced obesity by feeding the mice with western diet (containing high fat and carbohydrates) [ 21 ], and once the obesity was achieved, simvastatin was loaded to the obesogenic diet (Figure 1a for experimental design). At the end of the experiment, the weight of the mice on western diet was significantly increased compared to mice on standard diet (45.44 ± 1.34 gr versus 40.72 ± 2.15 gr, p = 0.04), whereas simvastatin addition to western diet did not have an impact on this parameter (46.83 ± 1.05 gr, p = 0.43).…”

Sexually dimorphic response of mice to the Western‐style diet caused by deficiency of fatty acid binding protein 6 (Fabp6)

“…The role of estrogen in regulating energy homeostasis and adiposity has been well established through inactivation of the Cyp19 (encodes aromatase) and Esr1 (encodes estrogen receptor α) genes in mice (Heine et al, 2000; Jones et al, 2000). However, an enhanced body weight gain phenomenon was also noticed in male Slc51a −/− mice (deficient in Ostα) compared to wild‐type mice fed the WSD (Hammond et al, 2015). It is more likely that the enhanced adiposity manifested by male Fabp6 −/− mice is a consequence of disrupted bile acid metabolism in the gut caused by the loss of Fabp6, although estrogen may mask this effect since female Fabp6 −/− mice did not show the same phenotype as male Fabp6 −/− mice.…”