Morgan Kengathevy, Uyuni Adhemar, Nandgiri Ganesh, Mao Lin, Castaneda Luciano, Kathirvel Elango, French Samuel W, Morgan Timothy R
Medical Services, VA Long Beach Healthcare System, Long Beach, California 90822, USA.
Eur J Gastroenterol Hepatol. 2008 Sep;20(9):843-54. doi: 10.1097/MEG.0b013e3282f9b203.
To determine whether expression of transcription factors and lipogenic enzymes is altered in liver and adipose tissue of mice with obesity, insulin resistance, and nonalcoholic fatty liver disease.
Mice were fed chow containing 9% of calories from standard fat (SF) or 20% of calories from high fat (HF) and killed after 9 months in the fasted or fed state.
Liver injury was evaluated by histology and serum aminotransferase levels. Transcription factor expression was measured by real-time PCR. Lipogenic enzymes were measured by real-time PCR and Western blots.
HF mice weighed more, had insulin resistance, hepatic steatosis, and focal pericellular hepatic fibrosis. Hepatic expression of sterol regulatory element-binding protein-1c, carbohydrate response element-binding protein, liver X receptor-alpha, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) decreased during fasting in SF and HF mice; however, FAS expression and protein content were higher in the liver of fasted HF mice than of fasted SF mice. In adipose tissue, expression of sterol response element-binding protein-1c, carbohydrate response element-binding protein, liver X receptor-alpha, peroxisome proliferator-activated receptor-gamma, ACC, and FAS decreased with fasting in mice fed SF, but not in HF mice. ACC and FAS expression and protein content remained higher during fasting in HF than in SF mice.
Feeding a nutritionally complete diet containing a moderate increase in fat produces obesity and steatohepatitis. During fasting, hepatic FAS expression and protein content are increased in HF mice. Transcription factor expression, and lipogenic enzyme expression and protein concentration do not decline during fasting in adipose tissue from HF mice. De-novo lipogenesis may persist in liver and adipose tissue during fasting in obesity/nonalcoholic fatty liver disease.
确定肥胖、胰岛素抵抗和非酒精性脂肪性肝病小鼠肝脏和脂肪组织中转录因子和生脂酶的表达是否发生改变。
给小鼠喂食含9%标准脂肪（SF）热量或20%高脂肪（HF）热量的食物，9个月后在禁食或进食状态下处死。
通过组织学和血清转氨酶水平评估肝损伤。通过实时PCR测量转录因子表达。通过实时PCR和蛋白质免疫印迹法测量生脂酶。
HF小鼠体重更重，有胰岛素抵抗、肝脂肪变性和局灶性细胞周围肝纤维化。在禁食期间，SF和HF小鼠肝脏中固醇调节元件结合蛋白-1c、碳水化合物反应元件结合蛋白、肝脏X受体α、乙酰辅酶A羧化酶（ACC）和脂肪酸合酶（FAS）的表达下降；然而，禁食的HF小鼠肝脏中FAS的表达和蛋白含量高于禁食的SF小鼠。在脂肪组织中，SF喂养的小鼠禁食时固醇反应元件结合蛋白-1c、碳水化合物反应元件结合蛋白、肝脏X受体α、过氧化物酶体增殖物激活受体γ、ACC和FAS的表达下降，但HF喂养的小鼠没有。在禁食期间，HF小鼠的ACC和FAS表达及蛋白含量仍高于SF小鼠。
喂食脂肪适度增加的营养完整饮食会导致肥胖和脂肪性肝炎。禁食期间，HF小鼠肝脏中FAS的表达和蛋白含量增加。HF小鼠脂肪组织禁食时转录因子表达、生脂酶表达和蛋白浓度不会下降。在肥胖/非酒精性脂肪性肝病禁食期间，肝脏和脂肪组织中可能持续存在从头脂肪生成。
