Metabolic imprinting induced by a high-sugar diet : efects on microRNA expression and insulin resistance in young rats.

Abstract

Background Metabolic imprinting describes associations between nutritional experiences of early life and the develop- ment of diseases later in life. The goal of this study was to evaluate the metabolic imprinting induced by a high-sugar diet

(HSD) and its efects on microRNA (miRNA) expression and insulin resistance (IR) in young rats. We assessed the efects of expression of adipogenic (miR-200c) and metabolic (miR-126a) miRNAs in retroperitoneal white adipose tissue (rWAT) on IR development. Methods and results Weaned male Wistar rats (N=6) were fed a standard chow diet or HSD (68% carbohydrates) for 4-, 8-,

or 12-weeks. Serum samples were collected to measure triacylglycerol and VLDL-cholesterol, and we assessed glucometa- bolic parameters (glucose, insulin, HOMA-IR, and QUICKI). rWAT was collected for microRNA analysis (N=3). The HSD

resulted in body fat accretion and IR after 8-weeks, which resolved by 12-weeks. Moreover, the HSD had a time-dependent efect on miRNA relative expression, downregulating rno-miR-200c-3p at week 8 and rno-miR-126a-3p at week 12. Conclusions MiR-200 family dysregulation has been related to IR, and miR-126a downregulation could be associated with

the improvement in IR observed after a 12-week HSD feeding period. This is the frst time that excessive sugar intake post- weaning has been associated with miRNA production by rWAT with an impact on IR development.