Abstract

Ancestral obesogenic exposure is able to trigger harmful effects in the offspring left ventricle (LV) which could lead to cardiovascular diseases. However, the impact of the father's lifestyle on the offspring LV is largely unexplored. The aim of this study was to investigate the effects of 8 weeks of paternal resistance training (RT) on the offspring left ventricle (LV) proteome exposed to control or high-fat (HF) diet. Wistar rats were randomly divided into two groups: sedentary fathers and trained fathers (8 weeks, 3 times per week with weights secured to the animals' tails). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into 4 groups (5 animals per group): offspring from sedentary fathers, exposed to control diet (SFO-C); offspring from trained fathers, exposed to control diet (TFO-C); offspring from sedentary fathers, exposed to high-fat diet (SFO-HF); and offspring from trained fathers, exposed to high-fat diet (TFO-HF). The LC-MS/MS analysis revealed 537 regulated proteins among groups. Offspring exposure to HF diet caused reduction in the abundance levels of proteins related to cell component organization, metabolic processes, and transport. Proteins related to antioxidant activity, transport, and transcription regulation were increased in TFO-C and TFO-HF as compared with the SFO-C and SFO-HF groups. Paternal RT demonstrated to be an important intervention capable of inducing significant effects on the LV proteome regardless of offspring diet due to the increase of proteins involved into LV homeostasis maintenance. This study contributes to a better understanding of the molecular aspects involved in transgenerational inheritance.

Highlights

  • Obesity is a chronic disease characterized by excessive fat deposition in adipocytes, while an interplay between many systems is implicated in obesity etiology, including unbalanced energy uptake, and energy expenditure, gene mutations, aberrant gut microbiota, and epigenetic factors [1]

  • Offspring left ventricle weight was modified by paternal training, as shown by decreased left ventricle weight in the TFO-C and TFO-HF groups as compared with the SFO-C and SFO-HF groups (p = 0:02 and p = 0:001, respectively)

  • Preconceptional paternal resistance training (RT) upregulates protein abundance levels related to myofibril components, cell processes, metabolic processes, antioxidant activity, transport, nucleosome assembly, translation, and transcription regulation on the left ventricle (LV) regardless of the offspring diet, which may be crucial for SFO-HF group X SFO-C group

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Summary

Introduction

Obesity is a chronic disease characterized by excessive fat deposition in adipocytes, while an interplay between many systems is implicated in obesity etiology, including unbalanced energy uptake, and energy expenditure, gene mutations, aberrant gut microbiota, and epigenetic factors [1]. Obesity has been associated with several deleterious effects, including functional disability, reduction in life expectancy, and increased mortality [3, 4]. Evidence from animal and human studies suggests that environmental perturbations, such as diet, stress, and drugs before birth, contribute to the development of permanent metabolic consequences in offspring and result in negative effects on phenotype [7]. Offspring from obese fathers showed an increase of gonadal adiposity and the harmful effects of sperm metabolic function when compared to offspring from healthy fathers. These perturbed offspring phenotypes were associated with modifications of fathers’ sperm microRNA content [10]

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