Glycaemic Index of Maternal Dietary Carbohydrate Differentially Alters Fto and Lep Expression in Offspring in C57BL/6 Mice

Nutrients. 2018 Sep 20;10(10):1342. doi: 10.3390/nu10101342.

Abstract

Maternal diet and gestational hyperglycaemia have implications for offspring health. Leptin (LEP) and fat mass and obesity-associated (FTO) alleles are known to influence body fat mass in humans, potentially via effects on appetite. We hypothesized that expression of Fto, Lep, and other appetite-related genes (Argp, Npy, Pomc, Cart, Lepr) in the offspring of female mice are influenced by the glycaemic index (GI) of carbohydrates in the maternal diet. C57BL/6 mice were randomly assigned to low or high GI diets and mated with chow-fed males at eight weeks of age. Male pups were weaned at four weeks and randomly divided into two groups, one group following their mother's diet (LL and HH), and one following the standard chow diet (LC and HC) to 20 weeks. Fto expression was 3.8-fold higher in the placenta of mothers fed the high GI diet (p = 0.0001) and 2.5-fold higher in the hypothalamus of 20-week old offspring fed the high GI (HH vs. LL, p < 0.0001). By contrast, leptin gene (Lep) expression in visceral adipose tissue was 4.4-fold higher in four-week old offspring of low GI mothers (LC vs. HC, p < 0.0001) and 3.3-fold higher in visceral adipose tissue of 20-week old animals (LL vs. HH, p < 0.0001). Plasma ghrelin and leptin levels, and hypothalamic appetite genes were also differentially regulated by maternal and offspring diet. These findings provide the first evidence in an animal model that maternal high GI dietary carbohydrates that are digested and absorbed faster may contribute to programming of appetite in offspring.

Keywords: C57BL/6; FTO; appetite; gene expression; glycaemic index; obesity; pregnancy.

MeSH terms

  • Agouti-Related Protein / metabolism
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / metabolism*
  • Animals
  • Dietary Carbohydrates / administration & dosage*
  • Dietary Carbohydrates / metabolism
  • Female
  • Gene Expression Regulation
  • Glycemic Index*
  • Hypothalamus / metabolism
  • Intra-Abdominal Fat / metabolism
  • Leptin / genetics
  • Leptin / metabolism*
  • Male
  • Maternal Nutritional Physiological Phenomena*
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism
  • Neuropeptide Y / metabolism
  • Nutritional Status*
  • Placenta / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Pro-Opiomelanocortin / metabolism
  • Receptors, Leptin / metabolism

Substances

  • Agouti-Related Protein
  • Agrp protein, mouse
  • Dietary Carbohydrates
  • Leptin
  • Nerve Tissue Proteins
  • Neuropeptide Y
  • Receptors, Leptin
  • cocaine- and amphetamine-regulated transcript protein
  • leptin receptor, mouse
  • Pro-Opiomelanocortin
  • FTO protein, mouse
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO