Department of Surgery and the Vascular Biology Program, Children's Hospital Boston and Harvard Medical School, Boston, MA, USA.
Metabolism. 2010 Aug;59(8):1092-105. doi: 10.1016/j.metabol.2009.11.006. Epub 2010 Jan 8.
Nonalcoholic fatty liver disease results from overconsumption and is a significant and increasing cause of liver failure. The type of diet that is conducive to the development of this disease has not been established, and evidence-based treatment options are currently lacking. We hypothesized that the onset of hepatic steatosis is linked to the consumption of a diet with a high fat content, rather than related to excess caloric intake. In addition, we also hypothesized that fully manifested hepatic steatosis could be reversed by reducing the fat percentage in the diet of obese mice. C57BL/6J male mice were fed either a purified rodent diet containing 10% fat or a diet with 60% of calories derived from fat. A pair-feeding design was used to distinguish the effects of dietary fat content and caloric intake on dietary-induced hepatic lipid accumulation and associated injury. Livers were analyzed by quantitative reverse transcriptase polymerase chain reaction for lipid metabolism-related gene expression. After 9 weeks, mice on the 60%-fat diet exhibited more weight gain, insulin resistance, and hepatic steatosis compared with mice on a 10%-fat diet with equal caloric intake. Furthermore, mice with established metabolic syndrome at 9 weeks showed reversal of hepatic steatosis, insulin resistance, and obesity when switched to a 10%-fat diet for an additional 9 weeks, independent of caloric intake. Quantitative reverse transcriptase polymerase chain reaction revealed that transcripts related to both de novo lipogenesis and increased uptake of free fatty acids were significantly up-regulated in mice pair-fed a 60%-fat diet compared with 10%-fat-fed animals. Dietary fat content, independent from caloric intake, is a crucial factor in the development of hepatic steatosis, obesity, and insulin resistance in the C57BL/6J diet-induced obesity model caused by increased uptake of free fatty acids and de novo lipogenesis. In addition, once established, all these features of the metabolic syndrome can be successfully reversed after switching obese mice to a diet low in fat. Low-fat diets deserve attention in the investigation of a potential treatment of patients with nonalcoholic fatty liver disease.
非酒精性脂肪性肝病是由过度摄入引起的，是肝衰竭的一个重要且日益增加的原因。导致这种疾病的饮食类型尚未确定，目前也缺乏基于证据的治疗选择。我们假设肝脂肪变性的发生与高脂肪含量的饮食有关，而不是与热量摄入过多有关。此外，我们还假设通过减少肥胖小鼠饮食中的脂肪百分比，可以逆转完全表现出的肝脂肪变性。雄性 C57BL/6J 小鼠分别喂食 10%脂肪的纯化啮齿动物饮食或 60%热量来自脂肪的饮食。采用配对喂养设计来区分饮食脂肪含量和热量摄入对饮食诱导的肝脂质堆积和相关损伤的影响。通过定量逆转录聚合酶链反应分析肝脏的脂质代谢相关基因表达。9 周后，与摄入等热量的 10%脂肪饮食的小鼠相比，摄入 60%脂肪饮食的小鼠体重增加更多，胰岛素抵抗和肝脂肪变性更为严重。此外，在 9 周时患有代谢综合征的小鼠，当切换到 10%脂肪饮食再喂养 9 周时，肝脂肪变性、胰岛素抵抗和肥胖均可逆转，与热量摄入无关。定量逆转录聚合酶链反应显示，与从头合成脂肪和游离脂肪酸摄取增加相关的转录物在喂食 60%脂肪饮食的小鼠中显著上调，与喂食 10%脂肪饮食的小鼠相比。独立于热量摄入，饮食中的脂肪含量是通过增加游离脂肪酸摄取和从头合成脂肪导致的 C57BL/6J 饮食诱导肥胖模型中肝脂肪变性、肥胖和胰岛素抵抗发展的关键因素。此外，一旦这些代谢综合征的所有特征建立后，肥胖小鼠切换到低脂肪饮食后都可以成功逆转。低脂饮食在研究非酒精性脂肪性肝病患者的潜在治疗方法中值得关注。
