Day-restricted feeding during pregnancy and lactation programs glucose intolerance and impaired insulin secretion in male rat offspring

Acta Physiol (Oxf). 2016 Jul;217(3):240-53. doi: 10.1111/apha.12684. Epub 2016 Apr 21.

Abstract

Aim: The maternal environment during pregnancy and lactation plays a determining role in programming energy metabolism in offspring. Among a myriad of maternal factors, disruptions in the light/dark cycle during pregnancy can program glucose intolerance in offspring. Out-of-phase feeding has recently been reported to influence metabolism in adult humans and rodents; however, it is not known whether this environmental factor impacts offspring metabolism when applied during pregnancy and lactation. This study aims to determine whether maternal day-restricted feeding (DF) influences energy metabolism in offspring.

Methods: Pregnant and lactating Wistar rats were subjected to ad libitum (AL) or DF during pregnancy and lactation. The offspring born to the AL and DF dams were intra- and interfostered, which resulted in 4 group types.

Results: The male offspring born to and breastfed by the DF dams (DF/DF off) were glucose intolerant, but without parallel insulin resistance as adults. Experiments with isolated pancreatic islets demonstrated that the male DF/DF off rats had reduced insulin secretion with no parallel disruption in calcium handling. However, this reduction in insulin secretion was accompanied by increased miRNA-29a and miRNA34a expression and decreased syntaxin 1a protein levels.

Conclusion: We conclude that out-of-phase feeding during pregnancy and lactation can lead to glucose intolerance in male offspring, which is caused by a disruption in insulin secretion capacity. This metabolic programming is possibly caused by mechanisms dependent on miRNA modulation of syntaxin 1a.

Keywords: lactation; metabolic programming; out-of-phase feeding; pregnancy.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Caloric Restriction / adverse effects*
  • Energy Metabolism / physiology
  • Female
  • Glucose Intolerance / metabolism
  • In Vitro Techniques
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / metabolism
  • Lactation / physiology*
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • NADP / metabolism
  • Pregnancy
  • Pregnancy, Animal / metabolism*
  • Rats
  • Rats, Wistar
  • Syntaxin 1 / biosynthesis
  • Syntaxin 1 / genetics

Substances

  • Insulin
  • MIRN29 microRNA, rat
  • MIRN34 microRNA, rat
  • MicroRNAs
  • Stx1a protein, rat
  • Syntaxin 1
  • NADP
  • Calcium