Adipose Gene Expression Patterns of Weight Gain Suggest Counteracting Steroid Hormone Synthesis

Abstract

To identify early molecular changes in weight gain, using analysis of gene expression changes in adipose tissue of mice fed well-defined humanized (Western) high-fat and low-fat (control) diets during a short (3- to 5-week) time interval. An adipose-enriched cDNA microarray was constructed and used for the expression analyses of visceral adipose tissues of wildtype young adult C57BL/6J male mice on different diets. Mice on a high-fat diet had significantly higher body weight (at most, 9.6% greater) and adipose tissue weights compared with mice on a control diet. Gene expression analyses revealed 31 transcripts significantly differentially expressed in visceral adipose tissue between the diet groups. Most of these genes were expressed more on the high-fat diet. They mainly encode proteins involved in cellular structure (e.g., myosin, procollagen, vimentin) and lipid metabolism (e.g., leptin, lipoprotein lipase, carbonic anhydrase 3). This increase in gene expression was accompanied by a decrease in oxidative phosphorylation and carbohydrate metabolism (ATP citrate lyase). Importantly, genes belonging to steroid hormone biosynthesis (3beta-hydroxysteroid dehydrogenase-1, cholesterol side-chain cleavage cytochrome P450, and steroid-11beta-hydroxylase) were all expressed less in mice on a high-fat diet. A short time period of 3 to 5 weeks of high-fat feeding altered gene expression patterns in visceral adipose tissue in male mice. Gene expression changes indicate initiation of adipose tissue enlargement and the down-regulation of adipose steroid hormone biosynthesis. The latter suggests a mechanism by which initial progression toward weight gain is counteracted.