Fish oil supplementation to rats fed high-fat diet during pregnancy prevents development of impaired insulin sensitivity in male adult offspring

Benjamin B Albert,Wayne S Cutfield,Clint Gray,Clare M Reynolds,Manohar L Garg,Paul L Hofman,José G B Derraik,Mark H Vickers,David Cameron-Smith,Stephanie A Segovia

doi:10.1038/s41598-017-05793-0

Benjamin B Albert, Wayne S Cutfield + Show 8 more

Open Access

https://doi.org/10.1038/s41598-017-05793-0

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Abstract

We examined whether maternal fish oil supplementation during pregnancy could prevent development of insulin resistance in adult male offspring of rat dams fed a high-fat diet. Time-mated Sprague-Dawley rat dams were randomised into four treatment groups: Con-Con, dams fed a control diet (fat: 15% kcal) and administered water by gavage; Con-FO, control diet with unoxidised fish oil by gavage; HF-Con, high-fat diet (fat: 45% kcal) and water by gavage; and HF-FO, high-fat diet and unoxidised fish oil by gavage. Dams were fed the allocated diet ad libitum during pregnancy and lactation, but daily gavage occurred only during pregnancy. After weaning, male offspring consumed a chow diet ad libitum until adulthood. Maternal high-fat diet led to increased food consumption, adiposity, systolic blood pressure, and triglycerides and plasma leptin in adult HF-Con offspring. HF-Con offspring also exhibited lower insulin sensitivity than Con-Con rats. Male offspring from HF-FO group were similar to HF-Con regarding food consumption and most metabolic parameters. However, insulin sensitivity in the HF-FO group was improved relative to the HF-Con offspring. Supplementation with unoxidised n-3 PUFA rich oils in the setting of a maternal obesogenic diet improved insulin sensitivity, but had no impact on body composition of adult male offspring.

Highlights

There has been a dramatic increase in the incidence of obesity and overweight worldwide[1]
Minimising the risk of oxidation is important, as in a parallel study we demonstrated that feeding highly oxidised fish oil to rat dams led to maternal insulin resistance and a substantial increase in neonatal mortality[32]
At the end of lactation, dams from the HF-Con group had similar energy intake to Con-Con dams, but had greater body weight (Fig. 2A) and retroperitoneal fat mass (Table 3). This was associated with greater fasting glucose (p = 0.018) and triglyceride (p = 0.047) concentrations, as well as a trend to greater insulin resistance (Table 3)

Summary

Introduction

There has been a dramatic increase in the incidence of obesity and overweight worldwide[1]. Maternal obesity appears to be the strongest predictor of offspring obesity[7], and even outside the obese range increasing pre-pregnancy body mass index is associated with greater adiposity and an adverse metabolic phenotype in the offspring[8]. This includes lower insulin sensitivity, an unfavourable adipokine profile, increased blood pressure and triglyceride concentrations[9, 10] and increased risk of type 2 diabetes and the metabolic syndrome[11]. This highlights pregnancy as a critical early window of opportunity where treatments that reduce fetal overnutrition may have lifelong benefit[14], potentially improving insulin sensitivity and in turn reducing the risk of type 2 diabetes and cardiovascular disease[15]

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