Paternal diet preconception changes child's metabolism into adulthood.

Read on to find out why.

The Background

We often think about genetics as a simple 1+1=2 equation. You inherit half your genes from your father, half from your mother, end of story. However, this isn’t the whole truth.

In addition to what becomes our DNA, we inherit other molecules like RNAs that play large roles in how our cells function, including the initial cells that we come from. These RNAs serve various purposes and affect the offspring into adulthood.

Mitochondria, famously known as the powerhouse of the cell, are inherited from the mother. This paper’s big finding is that while this is true, the RNAs we inherit from our fathers influence how our mitochondria function. Specifically, a paternal high fat diet prior to pregnancy can lead to mitochondrial dysfunction and a messed up metabolism, even into adulthood.

The Findings

It all comes back to the inherited RNAs. In mice, just 2 weeks of a high fat diet prior to conception led to altered RNAs and resulting glucose intolerance and insulin resistance in the kids. This somewhat shocked me. If it turns out to be true in humans, this means that a little 2 week sugar spree prior to conception can influence my future kids metabolism their whole life.

In mice, the authors found that this 2 week high fat diet prior to conception led to roughly 30% of offspring being glucose intolerant into adulthood (see the figure below, the higher number in the HFDi group = glucose intolerant). Interestingly, if the father mice were put on a normal diet for an additional 4 weeks after the high fat diet, their offspring showed no signs of glucose intolerance.

The data shows that short term dietary changes immediately before conception are enough to restore regular glucose and insulin tolerance. That’s a big deal. Even short term improvements in diet had a long term effect on the offspring.

The previously mentioned RNAs are at the heart of this diet-induced change. The authors found that many of the mitochondrial-related RNAs were affected by the diet changes, both in humans and in mice.

Interestingly, they found that this RNA inheritance occurred predominately among male mice offspring. Meaning, there was a much larger difference in glucose metabolism for the male offspring vs the female offspring. This indicates that the paternal preconception diet could disproportionately affect male offspring’s metabolism.

The scientists found that these paternal diet-induced effects were due to mitochondrial dysfunction. The father’s RNAs that were transferred to the offspring led to an early and improper switch in metabolism towards oxidative phosphorylation. Other studies have shown that similar switches in metabolism lead to alteration in mitochondrial function and eventually glucose intolerance, the same thing observed here.

To sum it all up, the paternal diet immediately preconception can influence their offspring’s metabolism well into adulthood. It can predispose the child to obesity while harming their glucose and insulin metabolism. On the bright side, at least in mice, even short term changes in diet can mitigate or eliminate this effect. Be careful what you eat if you’re in the market to have a kid!

See you next week for more science,

Neil