Submitted to: International Journal of Obesity
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/29/2009
Publication Date: 6/1/2010
Citation: Grove, K.L., Fried, S.K., Greenberg, A.S., Xiao, X.Q., Clegg, D.J. 2010. A mirccroarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice. International Journal of Obesity. 34(6):989-1000. Interpretive Summary: In this study we investigated the pattern of genes that are expressed in fat cells in male mice, and female mice who do make and who are unable to make female hormones on a high caloric diet that promotes obesity. We found that with the high caloric diet, the fat tissue of male mice had an increase in the genes that promote the expression of genes and protein normally associated with infection (inflammatory genes/proteins). While female mice tended to have reduced expression of genes and proteins associated with infection (inflammatory genes/proteins). Importantly, the expression of genes and proteins associated with infection (inflammatory genes/proteins) are thought to promote resistance to the antidiabetic actions of the hormone insulin and promote the risk of developing diabetes. These studies will direct researchers to investigate nutrients that reduce the expression of the genes and proteins associated with infection (inflammatory genes) to protect against developing resistance to insulin and therefore increased risk of developing diabetes.
Technical Abstract: A sexual dimorphism exists in body fat distribution; females deposit relatively more fat in subcutaneous/inguinal depots whereas males deposit more fat in the intra-abdominal/gonadal depot. Our objective was to systematically document depot- and sex-related differences in the accumulation of adipose tissue and gene expression, comparing differentially expressed genes in diet-induced obese mice with mice maintained on a chow diet. We used a microarray approach to determine whether there are sexual dimorphisms in gene expression in age-matched male, female or ovariectomized female (OVX) C57/BL6 mice maintained on a high-fat (HF) diet. We then compared expression of validated genes between the sexes on a chow diet. After exposure to a high fat diet for 12 weeks, females gained less weight than males. The microarray analyses indicate in intra-abdominal/gonadal adipose tissue in females 1642 genes differ by at least twofold between the depots, whereas 706 genes differ in subcutaneous/inguinal adipose tissue when compared with males. Only 138 genes are commonly regulated in both sexes and adipose tissue depots. Inflammatory genes (cytokine-cytokine receptor interactions and acute-phase protein synthesis) are upregulated in males when compared with females, and there is a partial reversal after OVX, where OVX adipose tissue gene expression is more 'male-like'. This pattern is not observed in mice maintained on chow. Histology of male gonadal white adipose tissue (GWAT) shows more crown-like structures than females, indicative of inflammation and adipose tissue remodeling. In addition, genes related to insulin signaling and lipid synthesis are higher in females than males, regardless of dietary exposure. These data suggest that male and female adipose tissue differ between the sexes regardless of diet. Moreover, HF diet exposure elicits a much greater inflammatory response in males when compared with females. This data set underscores the importance of analyzing depot-, sex- and steroid-dependent regulation of adipose tissue distribution and function.