Department of Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
Biol Pharm Bull. 2010;33(3):351-4. doi: 10.1248/bpb.33.351.
The liver is not a storage site of excess energy as triacylglycerides but a major site of carbohydrate storage, playing a vital role in glucose homeostasis, and the hepatic lipid droplets (LDs) should have a distinct physiologic role from those in lipid-storing tissues. Most studies so far have been limited to characterization of the LDs in cultured cells or of the liver of animals maintained on a normal laboratory diet, and little is known about the properties of the LDs in the liver responding to dietary excess, irregular fats, and potentially toxic compounds contained in a natural food diet. We started to characterize the hepatic LDs in wild-type and peroxisome proliferator-activated receptor alpha (PPARalpha)-null mice fed various natural diets by identifying the liver-enriched LD-associated proteins and the changes in lipid compositions. Based on the currently available data, we propose the hypothesis that hepatic LDs play vital protective roles against diet-derived excess fatty acids and potentially toxic hydrophobic compounds by temporarily storing them as neutral lipids or compounds until completion of the remodeling of fatty acids and detoxification of the compounds in a PPARalpha-dependent manner.
肝脏不是三酰甘油等多余能量的储存场所，而是碳水化合物储存的主要场所，在葡萄糖稳态中起着至关重要的作用，肝脂滴（LDs）应该具有与脂质储存组织中的 LDs 不同的生理功能。到目前为止，大多数研究都局限于培养细胞中 LDs 的特征描述或正常实验室饮食维持的动物肝脏的研究，而对于饮食过量、不规则脂肪和天然食物中潜在有毒化合物对肝脏 LDs 的特性知之甚少。我们开始通过鉴定肝脏富含 LD 的相关蛋白和脂质组成的变化，来描述野生型和过氧化物酶体增殖物激活受体α（PPARα）缺失小鼠在不同天然饮食下的肝脂滴。基于目前可用的数据，我们提出了一个假设，即肝脂滴通过以中性脂质或化合物的形式暂时储存它们，以防止饮食中多余的脂肪酸和潜在有毒的疏水性化合物，直到以 PPARα依赖的方式完成脂肪酸的重塑和化合物的解毒，从而发挥至关重要的保护作用。
