Metabolic syndrome is a prevalent disease resulting from an interplay of genomic component and the exposome. Parental diet has been shown to affect offspring metabolic health via multiple epigenetic mechanisms. Excess carbohydrate intake is one of the driving forces of the obesity and metabolic syndrome pandemics. This review summarizes the evidence for the effects of maternal carbohydrate (fructose, sucrose, glucose) overnutrition on the modulation of metabolic syndrome components in the offspring. Despite substantial discrepancies in experimental design, common effects of maternal carbohydrate overnutrition include increased body weight and hepatic lipid content of the "programmed" offspring. However, the administration of sucrose to several rat models leads to apparently favorable metabolic outcomes. Moreover, there is evidence for the role of genomic background in modulating the metabolic programming effect in the form of nutri-epigenomic interaction. Comprehensive, robust studies are needed to resolve the temporal, sex-specific, genetic, epigenetic and nutritional aspects of parental overnutrition in the intergenerational and transgenerational pathogenesis of metabolic syndrome.
Both prenatal and postnatal excessive consumption of dietary sucrose or fructose was shown to be detrimental to health and contributing to pathogenesis of metabolic syndrome. Our knowledge of genetic determinants of individual sensitivity to sucrose-driven metabolic effects is limited. In this study, we have tested the hypothesis that a variation of metabolic syndromerelated gene, Zbtb16 (Zinc Finger and BTB Domain Containing 16 will affect the reaction to high-sucrose diet (HSD) content in “matched” nutritional exposition settings, i.e. maternal HSD with re-exposition to HSD in adulthood vs. standard diet. We compared metabolic profiles of adult males of spontaneously hypertensive rats (SHR) and a single-gene, minimal congenic strain SHR-Zbtb16 fed either standard diet or exposed to HSD prenatally throughout gestation and nursing and again at the age of 6 months for the period of 14 days. HSD exposition led to increased adiposity in both strains and decrease of glucose tolerance and cholesterol (Ch) concentrations in majority of lowdensity lipoprotein (LDL) particle classes and in very large and large high-density lipoprotein (HDL) in SHR-Zbtb16 male offspring. There was a similar pattern of HSD-induced increase of triacylglycerols in chylomicrons and very low-density lipoprotein (VLDL) of both strains, though the increase of (triacylglycerol) TAG content was clearly more pronounced in SHR. We observed significant STRAIN*DIET interactions for the smallest LDL particles as their TAG content decreased in SHR-Zbtb16 and did not change in SHR in response to HSD. In summary, we provide evidence of nutrigenetic interaction between Zbtb16 and HSD in context of pathogenesis of metabolic syndrome.