Molecular mechanism driving retroperitoneal adipocyte hypertrophy and hyperplasia in response to a high-sugar diet.

Abstract

Scope: We have previously shown an increase in adipocyte size and lipid content in retroperitoneal white adipose tissue (rWAT) induced by an 8-week high-sugar diet (HSD). In this study, we assessed the effect of a HSD on the transcriptional activity of adipogenic genes in a timecourse study to provide insight regarding the genetic networks involved in the rWAT response to dietary sugar. Methods and results: Weaned male Wistar rats were fed a standard chow diet or HSD (68% carbohydrates) for 4, 8 or 12 weeks, and rWAT was removed for histopathology and PCR array (adipogenesis) analyses. The HSD induced adipocyte hypertrophy and hyperplasia in rWAT after 12 weeks of ingestion. Additionally, the HSD altered serum VLDL-cholesterol, triacylglycerol and glucometabolic parameters. Hierarchical clustering revealed HSD-induced changes in the expression patterns of the tested gene set. Pathway analysis, which used the enrichment analysis algorithm of the Thompson Reuters MetaCore platform, associated a cluster of differentially expressed genes with canonical pathways related to regulating adipocyte differentiation and proliferation (p-value < 10−7). Conclusion: HSD feeding post-weaning increased both the adipocyte size and number by simultaneously up-regulating pro-adipogenic signals (the PPAR pathway) and down-regulating anti-adipogenic signals (Wnt pathway) in young adults.