Sequential Responses to High-fat and High-calorie Feeding in an Obese Mouse Model

Objective: Reports on the immediate and long‐term responses to high‐fat and high‐calorie (HFC) feeding are controversial. Therefore, we examined the sequential effects of an HFC diet. Methods and Procedures: C57BL/6J mice were randomly assigned to consume either the control (C) or the HFC diet. Body weights and food intake were measured weekly and other measurements at weeks 2, 4, and 10. Microarrays were used for screening the transcriptional response of the livers at the three time points. Genes, encoding enzymes regulating key steps of lipid metabolism, were then selected from the microarray data for validation by quantitative real‐time reverse‐transcription polymerase chain reaction (qRT‐PCR) and their protein expression by western blot assays. Results: Mice fed with HFC diet for 2 weeks showed no increase in food intake and no difference in weight gain compared to the C mice. At weeks 4 and 10, the HFC mice increased their food intake and gained more weight than their controls (by 1.4 times and 2.5 times, respectively) (P < 0.01 at week 10). Genes involved in fatty acid oxidation (FAO) were initially upregulated and then downregulated, whereas the lipogenic genes and genes involved in cholesterol synthesis showed reverse trends. The differential mRNA expression of Cpt1L, Fas, and Hmgcr were confirmed by RT‐PCR and their protein expression by western blot assays. Discussion: Our findings suggested that when mice were fed an HFC diet, they could develop initial compensatory response to resist the increased energy balance; however, a prolonged consumption of an HFC diet appeared to disrupt this adaptation.