Short‐term, high fat feeding‐induced changes in white adipose tissue gene expression are highly predictive for long‐term changes

Abstract

We aimed to evaluate the predictability of short-term (5 days) changes in epididymal white adipose tissue (eWAT) gene expression for long-term (12 weeks) changes induced by high-fat diet (HFD) feeding. Mice were fed semisynthetic diets containing 10 (low-fat diet) or 40 (HFD) energy% of fat. Global gene expression in eWAT was analyzed using microarrays and confirmed by quantitative PCR. As expected, HFD feeding resulted in increased body fat accumulation and reduced glucose tolerance after 12 weeks. A total of 4678 transcripts were significantly changed by HFD after 12 weeks and 973 after 5 days, with an overlap of 764 transcripts encoding 549 genes. Of these, 79% were downregulated and 21% were upregulated by HFD, all in the same direction and highly correlated (r(2) = 0.90) between the time points. Pathway analysis showed downregulation of the main identified processes: lipid metabolism, carbohydrate metabolism, and oxidative phosphorylation. Mest (mesoderm-specific transcript) was highly upregulated, confirming its role as an early marker of fat cell expansion. The high predictive value of short-term gene expression changes for long-term effects of high fat feeding is a promising step to establish robust early biomarkers that could shorten animal trials to assess health-promoting food compounds.