Abstract

BackgroundThe paternal diet affects lipid metabolism in offspring for at least two generations through nutritional programming. However, we do not know how this is propagated to the offspring.ObjectivesWe tested the hypothesis that the changes in lipid metabolism that are driven by paternal diet are propagated through spermatozoa and not seminal plasma.MethodsWe applied an updated, purpose-built computational network analysis tool to characterise control of lipid metabolism systemically (Lipid Traffic Analysis v2.3) on a known mouse model of paternal nutritional programming.ResultsThe analysis showed that the two possible routes for programming effects, the sperm (genes) and seminal plasma (influence on the uterine environment), both have a distinct effect on the offspring’s lipid metabolism. Further, the programming effects in offspring suggest that changes in lipid distribution are more important than alterations in lipid biosynthesis.ConclusionsThese results show how the uterine environment and genes both affect lipid metabolism in offspring, enhancing our understanding of the link between parental diet and metabolism in offspring.

Highlights

  • The paternal diet affects lipid metabolism in offspring for at least two generations through nutritional programming

  • One important avenue is the evidence that lipid metabolism is clearly associated with nutritional programming (Furse et al, 2019, 2021b) and changes in lipid metabolism are associated with an increased risk of cardio-metabolic disease (CMD) (Cropley et al, 2016; Fernandez-Twinn et al, 2019; Ng et al, 2010; Perng et al, 2019; Wei et al, 2014)

  • The J of 0·78 and p of 0·48 shown in Fig. 2 showed that there were 6 additional species in the HH group (29:35, the number of variables for the control and experimental groups, respectively) and that both systems have isoforms of TG that appear throughout it that the other group does not. These results about TG metabolism showed that the differences in dietary intake by fathers caused nutritional programming of lipid metabolism and differences in the distribution of energy storage lipids

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Summary

Introduction

The paternal diet affects lipid metabolism in offspring for at least two generations through nutritional programming. One important avenue is the evidence that lipid metabolism is clearly associated with nutritional programming (Furse et al, 2019, 2021b) and changes in lipid metabolism are associated with an increased risk of cardio-metabolic disease (CMD) (Cropley et al, 2016; Fernandez-Twinn et al, 2019; Ng et al, 2010; Perng et al, 2019; Wei et al, 2014) Lipid metabolism is both shaped by nutritional programming and associated with metabolic ill-health, which suggests shared underlying mechanisms. The molecular changes that occur in the offspring as a result of that parental nutrition, such as their volume of adipose (Lecoutre & Breton, 2014; Lukaszewski et al, 2013) and hyperglycaemia (Fernandez-Twinn et al, 2019) Such effects have been investigated by network analysis of lipid metabolism (Furse et al, 2021b). Current evidence suggests that these two have separate effects(Li et al, 2016; McPherson et al, 2016; Morgan et al, 2020; Watkins & Sinclair, 2014; Watkins et al, 2017, 2018; Wei et al, 2014), a relationship with lipid metabolism has not been reported for either of them individually

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