Retinoic acid promotes tissue vitamin A status and modulates adipose tissue metabolism of neonatal rats exposed to maternal high-fat diet-induced obesity

J Nutr Sci. 2022 Jul 8:11:e54. doi: 10.1017/jns.2022.53. eCollection 2022.

Abstract

Maternal obesity may compromise the micronutrient status of the offspring. Vitamin A (VA) is an essential micronutrient during neonatal development. Its active metabolite, retinoic acid (RA), is a key regulator of VA homeostasis, which also regulates adipose tissue (AT) development in obese adults. However, its role on VA status and AT metabolism in neonates was unknown and it was determined in the present study. Pregnant Sprague-Dawley rats were randomised to a normal fat diet (NFD) or a high fat diet (HFD). From postnatal day 5 (P5) to P20, half of the HFD pups received oral RA every 3 d (HFDRA group). NFD pups and the remaining HFD pups (HFD group) received placebo. Six hours after dosing on P8, P14 and P20, n 4 pups per group were euthanised for different measures. It was found that total retinol concentration in neonatal liver and lung was significantly lower in the HFD group than the NFD group, while the concentrations were significantly increased in the HFDRA group. The HFD group exhibited significantly higher body weight (BW) gain, AT mass, serum leptin and adiponectin, and gene expression of these adipokines in white adipose tissue compared with the NFD group; these measures were significantly reduced in the HFDRA group. BAT UCP2 and UCP3 gene expression were significantly higher in pups receiving RA. In conclusion, repeated RA treatment during the suckling period improved the tissue VA status of neonates exposed to maternal obesity. RA also exerted a regulatory effect on neonatal obesity development by reducing BW gain and adiposity and modulating AT metabolism.

Keywords: Adipose tissue; BAT, brown adipose tissue; BW, body weight; HFD, high fat diet; LRAT, lecithin:retinol acyltransferase; Maternal obesity; NFD, normal fat diet; Neonatal lung; Neonatal obesity; Neonate; P, postnatal; RA, retinoic acid; RAR, retinoic acid receptor; RXR, retinoid X receptor; Retinoic acid; UCP, uncoupling protein; UPLC, ultra-high-performance liquid chromatography; VA, vitamin A; Vitamin A; WAT, white adipose tissue.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Animals, Newborn
  • Diet, High-Fat* / adverse effects
  • Female
  • Humans
  • Micronutrients
  • Obesity / metabolism
  • Obesity, Maternal*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Tretinoin / metabolism
  • Tretinoin / pharmacology
  • Vitamin A / pharmacology
  • Weight Gain

Substances

  • Micronutrients
  • Vitamin A
  • Tretinoin