Poster Topical Area: Nutrient-Gene Interactions
Location: Hall D
Poster Board Number: 451
Background: Chronic exposure to persistent organic pollutants (POPs) is associated with abnormal modifications in epigenetic regulation of glucose metabolism. This could induce the onset of insulin resistance and thus, the development of type 2 diabetes, with repercussions for subsequent generations. Furthermore, as a methyl donor, folic acid (FA) could counteract the abnormal epigenetic modifications induced by toxic environmental compounds. Objective: The objective was to examine whether FA supplementation in pregnant rats model exposed to POPs, at levels mimicking those observed in Quebec Great Northern population, improves glucose metabolism in male rats of the first and the two subsequent generations via paternal transmission.
Methods: Sprague-Dawley female rats (F0) were exposed by gavage to either an environmentally-relevant POPs mixture or a control solution. Gavage continued during mating to unexposed males and pregnancy and stopped after birth of the first generation (F1). Four treatments were administered to F0 females: control + diet including 2mg FA (n = 10), control + diet including 6mg FA (n = 10), POPs + diet including 2mg FA (n = 10), POPs + diet including 6mg FA (n = 10). Prenatally-treated F1 males were mated to untreated females to give birth to a second generation (F2) and then subsequently to a third generation (F3). After a 12h fast, a GTT was performed on F1, F2 and F3 males at 90 and 180 post-natal day (PND). Plasma glucose, insulin and C-peptide concentrations were measured at different time points (T=0, 15, 30, 60, 90, 120 min).
Results: In F1 males at PND90 (T=0), POPs increased plasma glucose. At PND180, an interaction POPs x FA (p=0.004) was observed on the IAUC molar insulin-to-C-peptide ratio, showing that FA counteracted the low hepatic insulin extraction observed with POPs. In F2 males at PND90, an interaction POPs x FA (p=0.05) was also observed. Specifically, FA counteracted the increase of plasma IAUC insulin observed with POPs.
Conclusion: Prenatal exposure to POPs without FA supplementation may cause abnormalities in plasma glucose and insulin concentrations and hepatic insulin extraction that are transmitted from generation to generation by the paternal lineage. FA supplementation may counteract deleterious effects of POPs.
Funding Source: Supported by CIHR
School of Nutrition and INAF, Laval University
Quebec, Quebec, Canada