Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an "obesogenic" diet - Beyond the Abstract

As obesity is becoming increasingly prevalent globally, it also increases the chances that both a father and his son will share the same ‘obesogenic’ diet, especially considering that dietary habits are often learnt from parents. Therefore we modelled this situation in mice by using a high fat diet, specifically designed to imitate a western style fast-food diet, whereby male offspring were exposed to the same high fat diet as their fathers.

The 2x2 experimental design of our dietary regimens saw founder males and their offspring fed either a high fat diet or a nutritionally matched control diet. Consistent with findings from previous studies a pre-conception paternal exposure to a high fat diet impaired the metabolic and reproductive health of male offspring, despite them being fed a control diet. However, on summary of all measures, we found that male offspring from fathers fed a high fat diet have a heightened susceptibility to metabolic and reproductive derangements induced by the same diet.

Specifically male offspring sired by a high fat diet fed male that were also fed the same high fat diet were the heaviest, had the greatest adiposity and had the greatest concentration of serum cholesterol, triglyceride, HDL and NEFA compared with CD sired/fed littermates. A synergistic increase in fasted serum insulin was unmasked by the combination of father/son high fat diet consumption, concomitant with increased fasted sera glucose only observed in these animals. Furthermore the concentrations of reactive oxygen species in sperm and sperm-oocyte binding saw detrimental effects of both a father’s high fat diet and a son’s high fat diet with a statistical interaction evident between both, culminating in the most impaired sperm parameters in this group. Whereas either a father’s or a son’s high fat diet by itself was associated with similar reductions to offspring sperm motility, without any further detriment observed as a combination of both father/son consuming the high fat diet.

Interestingly in regards to sperm motility the male offspring that fared worst were those born to high fat diet fed fathers that then consumed the control diet themselves. This perhaps suggests that paternal programming might have a somewhat protective effect in F1 male offspring when exposed to the same high fat diet, or that for sperm motility that a father/son dietary mismatch might be most detrimental. Furthermore the consumption of a high fat diet by males born to high fat diet fed fathers led to a smaller increase in oxidative stress and smaller decrease to sperm binding when compared to those born to control diet fed fathers. Whether these sperm measures provide evidence of a predictive adaptive response warrants further investigation.

In summary this indicates that metabolic and fertility disturbances in male offspring sired by fathers fed a high fat diet are exacerbated by a ‘second-hit’ of their own exposure to the same obesogenic environment. If these findings are translatable to human health, it suggests that adverse reproductive and metabolic outcomes may be amplified across generations due to the consumption of a common calorie dense diet, and might predict sombre outcomes for human health considering the current worldwide obesity epidemic.

Written by:
Tod Fullston
Discipline of Obstetrics & Gynaecology, Robinson Research Institute, Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.

Abstract: Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an "obesogenic" diet

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