Sex Differences in Early Programming by Maternal High Fat Diet Induced-Obesity and Fish Oil Supplementation in Mice.

Latha Ramalingam,Stephani Spainhour,Kalhara R Menikdiwela,Tochi Eboh,Naima Moustaid-Moussa

doi:10.3390/nu13113703

Abstract

Pre-pregnancy obesity is a contributing factor for impairments in offspring metabolic health. Interventional strategies during pregnancy are a potential approach to alleviate and/or prevent obesity and obesity related metabolic alterations in the offspring. Fish oil (FO), rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) exerts metabolic health benefits. However, the role of FO in early life remains still unknown. Hence, this study objective was to determine the effect of FO supplementation in mice from pre-pregnancy through lactation, and to study the post-natal metabolic health effects in gonadal fat and liver of offspring fed high fat (HF) diet with or without FO. Female C57BL6J mice aged 4–5 weeks were fed a HF (45% fat) diet supplemented with or without FO (30 g/kg of diet) and low fat (LF; 10% fat) pre-pregnancy through lactation. After weaning, offspring (male and female) from HF or FO dams either continued the same diet (HF-HF and FO-FO) or switched to the other diet (HF-FO and FO-HF) for 13 weeks, creating four groups of treatment, and LF-LF was used as a control group. Serum, gonadal fat and liver tissue were collected at termination for metabolic analyses. Offspring of both sexes fed HF with or without fish oil gained (p < 0.05) more weight post weaning, compared to LF-LF-fed mice. All the female offspring groups supplemented with FO had reduced body weight compared to the respective male groups. Further, FO-FO supplementation in both sexes (p < 0.05) improved glucose clearance and insulin sensitivity compared to HF-HF. All FO-FO fed mice had significantly reduced adipocyte size compared to HF-HF group in both male and females. Inflammation, measured by mRNA levels of monocyte chemoattractant protein 1 (Mcp1), was reduced (p < 0.05) with FO supplementation in both sexes in gonadal fat and in the liver. Markers of fatty acid synthesis, fatty acid synthase (Fasn) showed no sex specific differences in gonadal fat and liver of mice supplemented with HF. Female mice had lower liver triglycerides than male counterparts. Supplementation of FO in mice improved metabolic health of offspring by lowering markers of lipid synthesis and inflammation.

Highlights

We observed that the pre-pregnancy weights of high fat (HF) and Fish oil (FO) dams were significantly different from low fat (LF) fed dams, but there was no difference between the HF and FO dams (Figure S1A)
Food intake was lower in all the groups supplemented with HF compared to LF-LF
This study identified that FO supplementation during pregnancy was beneficial, even when offspring were challenged with HF

Summary

Introduction

Obesity prevalence in pregnant women and children, are alarmingly rising in the United States and globally [1,2,3,4]. Whilst lifestyle and diet are known to contribute to obesity, other factors that include genetic and environmental components play a critical role in its development [5,6]. Pre-pregnancy obesity affects the offspring’s future health by increasing the risk of metabolic disorders [7,8,9]. Both animal and human studies collectively indicate that excess supply of energy in the in-utero environment affects metabolic phenotype in part by excess accumulation of fat in the offspring [9,10]

Methods

Results

Conclusion