Journal Article

A maternal high-fat, high-sucrose diet alters insulin sensitivity and expression of insulin signalling and lipid metabolism genes and proteins in male rat offspring: effect of folic acid supplementation

Ramdath, D. Dan, Cuthbert, Candace E., Foster, Jerome E.

2017

Overview

A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid homoeostasis through unknown mechanisms and may be modulated by folic acid. We investigated the effect of a maternal HFS diet on glucose homoeostasis, expression of genes and proteins associated with insulin signalling and lipid metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male rat offspring. Pregnant Sprague–Dawley rats were randomly fed control (CON), HFS or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma insulin and glucose and liver and skeletal muscle gene and protein expression were measured. Treatment effects were assessed by one-way ANOVA. Maternal HFS diet induced higher fasting glucose in offspring v. HFS/F (P=0·027) and down-regulation (P<0·05) of genes coding for v-Akt murine thymoma viral oncogene homolog 2, resistin and v-Raf-1 murine leukaemia viral oncogene homolog 1 (Raf1) in offspring skeletal muscle and acetyl-CoA carboxylase (Acaca), fatty acid synthase and phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit β in offspring liver. Skeletal muscle neuropeptide Y and hepatic Kruppel-like factor 10 were up-regulated in HFS v. CON offspring (P<0·05). Compared with CON, Acaca and Raf1 protein expression levels were significantly lower in HFS offspring. Maternal HFS induced higher homoeostasis model of assessment index of insulin resistance v. CON (P=0·030) and HFS/F was associated with higher insulin (P=0·016) and lower glucose (P=0·025). Maternal HFS diet alters offspring insulin sensitivity and de novo hepatic lipogenesis via altered gene and protein expression, which appears to be potentiated by folate supplementation.

• Publisher: Cambridge University Press
• Subject: Acetyl-CoA carboxylase / Acetyl-CoA Carboxylase - genetics / Acetyl-CoA Carboxylase - metabolism / AKT protein / analysis of variance / Animals / Animals, Newborn / Blood Glucose - metabolism / Diabetes / Diet / Diet, High-Fat / Dietary supplements / Down-Regulation / Epigenetics / Fasting / Fatty Acid Synthases - genetics / Fatty Acid Synthases - metabolism / Fatty-acid synthase / Female / Folic acid / Folic Acid - administration & dosage / gene expression / gene expression regulation / Genes / Glucose / high carbohydrate diet / Insulin / Insulin - blood / Insulin Resistance / Kinases / Krueppel-like factor / laboratory animals / Leukemia / Lipid Metabolism / Lipids / Lipogenesis / Liver / Liver - metabolism / Male / Males / Maternal Nutritional Physiological Phenomena / mice / Molecular Nutrition / Muscles / Neural coding / Neuropeptide Y / Offspring / oncogenes / Phosphotransferases (Alcohol Group Acceptor) - genetics / Phosphotransferases (Alcohol Group Acceptor) - metabolism / Pregnancy / Prenatal experience / Prenatal Exposure Delayed Effects / progeny / protein subunits / protein synthesis / Proteins / Proto-Oncogene Proteins c-akt - genetics / Proto-Oncogene Proteins c-akt - metabolism / Proto-Oncogene Proteins c-raf - genetics / Proto-Oncogene Proteins c-raf - metabolism / Raf protein / Rats / Rats, Sprague-Dawley / resistin / Resistin - genetics / Resistin - metabolism / Rodents / Sensitivity / Skeletal muscle / Sucrose / Sugar / Thymoma / Up-Regulation / Variance analysis / Weaning