Hammond Christine L, Wheeler Sadie G, Ballatori Nazzareno, Hinkle Patricia M
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York, USA.
Department of Pharmacology and Physiology, University of Rochester School of Medicine, Rochester, New York, USA.
Physiol Rep. 2015 Jan 27;3(1). doi: 10.14814/phy2.12263. Print 2015 Jan 1.
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.
有机溶质转运体α-OSTβ是一种胆汁酸转运体，对肠肝循环中的胆汁酸循环至关重要。与野生型小鼠相比，Ostα(-/-)小鼠的胆汁酸池较小，粪便脂质增加，并且对与年龄相关的体重增加和胰岛素抵抗具有相对抗性。这些研究测试了Ostα(-/-)小鼠是否也能免受高脂肪和高胆固醇西式饮食（WD）通常会导致的体重增加、脂质变化和胰岛素抵抗的影响。野生型和Ostα(-/-)小鼠分别喂食WD、对照低脂饮食（LF）或标准实验室饲料（CH）。令人惊讶的是，尽管Ostα(-/-)小鼠在LF和CH饮食下体重仍然较轻，但在WD饮食12周后，它们的体重与野生型小鼠相同，尽管胆汁酸池水平仍然较低，粪便脂质排泄仍然较高。当从CH转换为LF或WD时，两种基因型的小鼠脂质排泄相对减少。WD对Ostα(-/-)小鼠小肠中参与脂质转运的基因表达的影响比野生型小鼠略大，但最大的差异存在于CH和特定饮食之间。喂食WD后，Ostα(-/-)小鼠的血清胆固醇和肝脏脂质较低，但Ostα(-/-)和野生型小鼠的肌肉脂质水平相当，在葡萄糖和胰岛素耐受性测试中的反应相似。综上所述，结果表明，尽管胆汁酸水平较低，Ostα(-/-)小鼠仍能够适应西式饮食。
