DNA microarray analysis of genes differentially expressed in diet-induced (cafeteria) obese rats.

Objective: To better understand the molecular basis of dietary obesity, we examined adipose tissue genes differentially expressed in an obesity model using DNA microarray analysis. Research Methods and Procedures: We assessed the expression level of over 12,500 transcripts in epididymal fat pads from (cafeteria) obese and control rats with the aid of the array technology. Results: Cafeteria (obese) rats weighed 50% more and had 2.5-fold higher levels of epididymal fat and elevated levels of circulating leptin. Adipose genes differentially expressed in obese and control rats were categorized into five groups: macronutrient metabolism, transcription factors, hormone receptor and signal transduction, redox and stress proteins, and cellular cytoskeleton. Interestingly, the expression levels of a number of genes involved in lipid metabolism such as glycerol-3-phosphate dehydrogenase, stearoyl coenzyme A desaturase, together with the transcription factors implicated in adipocyte differentiation (CAAT/enhancer binding protein-alpha and peroxisome proliferator-activated receptor-gamma), were significantly increased in obese animals compared with control. The most up-regulated transcripts were the ob (49.2-fold change) and the fatty acid-binding protein genes (15.7- fold change). In contrast, genes related to redox and stress protein were generally down-regulated in obese animals compared with the control. Discussion: Our study showed that in diet-induced obesity, the expression levels of some important genes implicated in lipid metabolism were up-regulated, whereas those related to redox and stress protein were down-regulated in obese animals compared with control. This pattern of gene expression may occur in human obesity cases after high-fat intake