The organic solute transporter alpha-beta (OSTα-OSTβ) is one of the newest members of the solute carrier family, designated as SLC51, and arguably one of the most unique. The transporter is composed of two gene products encoded by SLC51A and SLC51B that heterodimerize to form the functional transporter complex. SLC51A encodes OSTα, a predicted 340-amino acid, 7-transmembrane (TM) domain protein, whereas SLC51B encodes OSTβ, a putative 128-amino acid, single-TM domain polypeptide. Heterodimerization of the two subunits increases the stability of the individual proteins, facilitates their post-translational modification, and is required for delivery of the functional transporter complex to the plasma membrane. There are no paralogues for SLC51A or SLC51B in any genome that has been examined. The transporter functions via a facilitated diffusion mechanism, and can mediate either efflux or uptake depending on the electrochemical gradient of its substrates. Overall, characterization of the transporter's substrate specificity, transport mechanism, tissue distribution, subcellular localization, and transcriptional regulation as well as the phenotype of the recently generated Slc51a-deficient mice have revealed that OSTα-OSTβ plays a central role in the transport of bile acids, conjugated steroids, and structurally-related molecules across the basolateral membrane of many epithelial cells. In particular, OSTα-OSTβ appears to be essential for intestinal bile acid absorption, and thus for dietary lipid absorption.
Ϫ/Ϫ mice exhibit altered expression of intestinal lipid absorption genes, resistance to age-related weight gain, and modestly improved insulin sensitivity. Am
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.
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