The Impact of Administration of Fenofibrate During Suckling on Glucose Homeostasis and Programming of Metabolic Function in Adolescent Sprague Dawley Rats

Abstract

Fenofibrate, a PPAR α agonist used in the treatment of hyperlipidaemia is known to prevent diabetes and its complications. It is cautiously used during pregnancy and in neonates due to its potential for teratogenesis. The suckling period is a critical window for developmental programming. Drugs with antimetabolic syndrome activities have been used during critical developmental periods to program for protection against metabolic syndrome or its components. We evaluated the long-term metabolic effects of fenofibrate when administered during suckling and whether it would prevent the poor metabolic outcomes associated with high fructose intake in adolescent rats. A total of 119, 6-day-old (male and female) Sprague Dawley pups were randomly allocated to four groups and either orally gavaged with 10ml.kg-1 DMSO (0.5%), 100mg.kg-1 fenofibrate, 20% (w/v) fructose or both fructose and fenofibrate till 21 days after birth (PND) 21. Following weaning onto standard commercial rat cubes, the groups were split up further into two based on their drinking fluid: either fructose (20%, w/v) or tap water till PND 63 when they were subjected to an overnight fast before being terminated. Blood was taken for hormone analysis. The kidneys, pancreas, liver and visceral fat pad were weighed. Hepatic tissue was stored at -20ºC until quantification of hepatic fat content. Although the rats gained weight significantly (p<0.0001) throughout the study period, there were no significant differences in terminal body weights across the groups (p>0.05). The interventions did not significantly (p>0.05) alter concentrations of blood glucose, adiponectin and insulin. In both sexes, the HOMA-IR, liver lipids and visceral masses were similar in the different treatment groups. Fenofibrate administered to suckling rats did not adversely impact health of the study rats. It may therefore be safe for use in neonates.