Dietary oleic acid regulates hepatic lipogenesis through a liver X receptor-dependent signaling

Olive oil consumption is beneficial for health as it is associated with a decreased prevalence of cancer and cardiovascular diseases. Oleic acid is, by far, the most abundant component of olive oil. Since it can be made through de novo synthesis in animals, it is not an essential fatty acid. While it has become clear that dietary oleic acid regulates many biological processes, the signaling pathway involved in these regulations remains poorly defined. In this work we tested the impact of an oleic acid-rich diet on hepatic gene expression. We were particularly interested in addressing the contribution of Liver X Receptors (LXR) in the control of genes involved in hepatic lipogenesis, an essential process in whole body energy homeostasis. We used wild-type mice and transgenic mice deficient for both α and β Liver X Receptor isoforms (LXR-/-) fed a control or an oleate enriched diet. We observed that hepatic-lipid accumulation was enhanced as well as the expression of lipogenic genes in the liver of wild-type mice fed the oleate enriched diet. In contrast, none of these changes occurred in the liver of LXR-/- mice. Strikingly, oleate-rich diet reduced cholesterolemia in wild-type mice and induced signs of liver inflammation and damage in LXR-/- mice but not in wild-type mice. This work suggests that dietary oleic acid reduces cholesterolemia while promoting LXR-dependent hepatic lipogenesis without detrimental effects to the liver.

橄榄油摄入有益于健康，因其与癌症及心血管疾病患病率降低密切相关。油酸是橄榄油中含量最为丰富的组分。由于动物体内可通过从头合成途径生成油酸，因此油酸并非必需脂肪酸。尽管已有研究明确膳食油酸可调控多种生物学过程，但其介导此类调控的信号通路仍未得到充分阐明。本研究探究了高油酸膳食对肝脏基因表达的影响。我们重点关注肝X受体（Liver X Receptors, LXR）在调控肝脏脂肪生成相关基因中的作用——肝脏脂肪生成是维持全身能量稳态的关键过程。我们选用野生型小鼠，以及同时敲除α和β两种肝X受体亚型的转基因小鼠（LXR-/-），分别喂食对照膳食或高油酸膳食。我们观察到，喂食高油酸膳食的野生型小鼠，其肝脏脂质积累与脂肪生成相关基因的表达均出现上调。相比之下，LXR-/-小鼠的肝脏并未出现上述任何变化。值得注意的是，高油酸膳食可降低野生型小鼠的血胆固醇水平，却会在LXR-/-小鼠中诱发肝脏炎症与损伤征象，而野生型小鼠则无此表现。本研究结果表明，膳食油酸可降低血胆固醇水平，同时通过依赖肝X受体的途径促进肝脏脂肪生成，且不会对肝脏造成不良影响。