Altered expression of transcription factors and genes regulating lipogenesis in liver and adipose tissue of mice with high fat diet-induced obesity and nonalcoholic fatty liver disease.

OBJECTIVE

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.

METHODS

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.

MEASUREMENTS

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.

RESULTS

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.

CONCLUSION

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.