Maternal under-nutrition during pregnancy alters the molecular response to over-nutrition in multiple organs and tissues in nonhuman primate juvenile offspring

J Dev Orig Health Dis. 2024 Nov 7:15:e27. doi: 10.1017/S2040174424000163.

Abstract

Previous studies in rodents suggest that mismatch between fetal and postnatal nutrition predisposes individuals to metabolic diseases. We hypothesized that in nonhuman primates (NHP), fetal programming of maternal undernutrition (MUN) persists postnatally with a dietary mismatch altering metabolic molecular systems that precede standard clinical measures. We used unbiased molecular approaches to examine response to a high fat, high-carbohydrate diet plus sugar drink (HFCS) challenge in NHP juvenile offspring of MUN pregnancies compared with controls (CON). Pregnant baboons were fed ad libitum (CON) or 30% calorie reduction from 0.16 gestation through lactation; weaned offspring were fed chow ad libitum. MUN offspring were growth restricted at birth. Liver, omental fat, and skeletal muscle gene expression, and liver glycogen, muscle mitochondria, and fat cell size were quantified. Before challenge, MUN offspring had lower body mass index (BMI) and liver glycogen, and consumed more sugar drink than CON. After HFCS challenge, MUN and CON BMIs were similar. Molecular analyses showed HFCS response differences between CON and MUN for muscle and liver, including hepatic splicing and unfolded protein response. Altered liver signaling pathways and glycogen content between MUN and CON at baseline indicate in utero programming persists in MUN juveniles. MUN catchup growth during consumption of HFCS suggests increased risk of obesity, diabetes, and cardiovascular disease. Greater sugar drink consumption in MUN demonstrates altered appetitive drive due to programming. Differences in blood leptin, liver glycogen, and tissue-specific molecular response to HFCS suggest MUN significantly impacts juvenile offspring ability to manage an energy rich diet.

Keywords: Developmental programming; intrauterine growth restriction; nonhuman primate; western diet.

MeSH terms

  • Animals
  • Female
  • Fetal Development
  • Liver / metabolism
  • Male
  • Malnutrition*
  • Maternal Nutritional Physiological Phenomena*
  • Overnutrition / metabolism
  • Papio*
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / metabolism