Maternal but Not Paternal High-Fat Diet (HFD) Exposure at Conception Predisposes for 'Diabesity' in Offspring Generations.

Karen Schellong,Andreas Plagemann,Kerstin Melchior,Thomas Ziska,Wolfgang Henrich,Rebecca C Rancourt

doi:10.3390/ijerph17124229

Abstract

While environmental epigenetics mainly focuses on xenobiotic endocrine disruptors, dietary composition might be one of the most important environmental exposures for epigenetic modifications, perhaps even for offspring generations. We performed a large-scale rat study on key phenotypic consequences from parental (F0) high-caloric, high-fat diet (HFD) food intake, precisely and specifically at mating/conception, focusing on ‘diabesity’ risk in first- (F1) and second- (F2) generation offspring of both sexes. F0 rats (maternal or paternal, respectively) received HFD overfeeding, starting six weeks prior to mating with normally fed control rats. The maternal side F1 offspring of both sexes developed a ‘diabesity’ predisposition throughout life (obesity, hyperleptinemia, hyperglycemia, insulin resistance), while no respective alterations occurred in the paternal side F1 offspring, neither in males nor in females. Mating the maternal side F1 females with control males under standard feeding conditions led, again, to a ‘diabesity’ predisposition in the F2 generation, which, however, was less pronounced than in the F1 generation. Our observations speak in favor of the critical impact of maternal but not paternal metabolism around the time frame of reproduction for offspring metabolic health over generations. Such fundamental phenotypic observations should be carefully considered in front of detailed molecular epigenetic approaches on eventual mechanisms.

Highlights

Obesity and diabetes (‘diabesity’) are critical health challenges in westernized countries, globally, while genuine and effective measures of primary prevention are rare
Female outbred Wistar rats aged 120–130 days were randomly assigned to two groups paired for body weight and were exposed to either standard chow diet (Controls, C; n = 7, 13.0 MJ/kg, energy 9% fat, 33% protein, 58% carbohydrates, ssniff R/M-H, Soest, Germany, Code V1534-000) or high-fat diet (HFD; n = 5, 17.2 MJ/kg, energy 34% fat, 23% protein, 43% carbohydrates, specific diet, Code 132006; Altromin, Lage, Germany)
Maternal HFD exposure gave rise to increased risk in offspring generations while, in contrast, no increased ‘diabesity’ risk was observed in the offspring due to paternal HFD exposure

Summary

Introduction

Obesity and diabetes (‘diabesity’) are critical health challenges in westernized countries, globally, while genuine and effective measures of primary prevention are rare. High caloric food intake belongs to the key challenges for public health efforts related to diabetes and overweight prevention [1]. Overweight and overnutrition are the main diabetogenic risk factors at reproductive age, in general, while gestational overweight/obesity (>30%) and gestational diabetes mellitus (GDM; >10%) are reaching epidemic prevalence [2,3,4]. Numbers of clinical and experimental studies have shown that a predisposition to develop ‘diabesity’ may be ‘programed’ through exposure to diabetic and affluent developmental conditions already in utero and early life [5,6,7]. Maternal obesity and accompanying gestational diabetes have been. Public Health 2020, 17, 4229; doi:10.3390/ijerph17124229 www.mdpi.com/journal/ijerph

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