Repeated Retinoic Acid Treatments Modulate Adipose Tissue Development of Neonatal Rats Reared by Mothers Consuming a High Fat Diet

Abstract

Abstract Objectives Retinoic acid (RA), the active metabolite of vitamin A, has been shown to be a regulator of adipose tissue (AT) development in adult models. The aim of the study was to assess the effects of repeated RA treatments on body weight (BW) gain, AT development, and metabolic conditions of neonatal rats reared by mothers consuming a high-fat diet (HFD). Methods Five Sprague-Dawley rats arrived on their second day of gestation and were randomized to either a normal-fat diet (NFD = 25% fat; n = 2) or a HFD (50% fat; n = 3) both with a marginal level of VA at 0.35 mg/kg. Half of the pups delivered by mothers in HFD cohort received oral RA treatments. Specifically, on postnatal day 5 (P5) and P8, respectively, n = 12 pups in HFD cohort received an oral RA dose at 4 μg/g BW (HFD + RA group). Remaining pups in HFD cohort (n = 12; HFD group) and pups in NFD cohort (n = 12; NFD group) both received oil as placebo. Six hours after the dose administration on P8, n = 4 pups/group were euthanized with blood, visceral white AT (WAT), and brown AT (BAT) collected. On P11 and P14, remaining pups in NFD, HFD, and HFD + RA group (n = 8/group) received a dose of oil, oil, and RA, respectively. Six hours after the administration on P14, n = 4 pups/group were sacrificed. On P17 and P20, remaining pups in each group (n = 4) received their respective treatment and were euthanized six hours afterwards on P20. Serum samples from P14 and P20 sacrifice were analyzed for concentrations of glucose, insulin, lipids, adipokines, and inflammatory markers. Results At P8 and P14, no significant difference in BW gain, WAT mass, and BAT mass of pups was noted among groups. At P20, all three measures were significantly (P < 0.05) higher in the HFD group than in the NFD group; the measures were significantly decreased in the HFD + RA group compared to the HFD group. At P20, serum adiponectin and leptin concentrations were both significantly higher in the HFD than in the NFD group; RA treatment significantly reduced the concentrations of both. The pattern of changes in serum leptin was also observed at P14. At both P14 and P20, serum triglyceride was found to be significantly higher in pups receiving RA treatment. Conclusions Repeated RA treatments exerted a regulatory role on the AT metabolism and development of neonatal offspring to mothers consuming a HFD, as evidenced by reduced BW gain and AT mass as well as modulation of adipokines. Funding Sources NIH.