The Code for Obesity – Written in the Sperm
Finally some focus on the importance of paternal health! There’s LOTS of research on the effect of a mother’s health (and even grandmother’s health) on her child, particularly with regard to obesity. In fact, when using the search terms “maternal health, obesity, children” on PubMed, nearly 2k publications popped up. Using the same search terms, but swapping out “maternal” for “paternal,” only 160 studies fit the bill.
However, new research published last week in Cell Metabolism adds to the relatively small body of literature focusing on paternal health. You may have seen this in the headlines as the Washington Post declared that obesity “makes sperm weird” (insert image of writers in the WP newsroom giggling like schoolchildren).
I don’t want to give these sperm a complex, so let’s not call them “weird.” They’re just different. But they are different in potentially very important ways that have to do with epigenetics.
As a brief background, epigenetics is the study of how a cell regulates what genes are turned on or off based on external or environmental factors. That is, a person’s gene’s don’t change, but whether those genes get expressed is often a matter of environmental influences (i.e. diet, physical activity, pollution, etc.). Additionally, there’s a plethora of research about how epigenetic codes from a parent can influence a child’s gene expression. One important epigenetic signal is DNA methylation. In general, when genes are methylated, they are locked in the “off” position, and this is important for a number of processes including embryonic development and cell differentiation.
The study in question by Donkin, et al. evaluated the epigenetic signatures in sperm samples from lean men (n=13) and men with obesity and poor glucose control (n=10), as well as from men with Type III Obesity (BMI ≥40.0 kg/m²; n=6) before and after undergoing gastric bypass surgery. Previous work indicates that children of obese fathers have an increased risk of developing metabolic diseases. The authors point out that this phenomenon is not simply due to behavioral traits that a child learns from a parent or socioeconomic status, as this effect has been observed in rodent studies as well as epidemiological studies where SES can be controlled for. What the researchers found in this study is that DNA methylation profiles in sperm from men with obesity are distinctly different from lean men. Importantly, many of these differences in methylation were related to genes that govern processes like appetite regulation as well as those linked to obesity and fat mass. Furthermore, a week after undergoing gastric bypass, methylation of over 1,500 genes were changed in sperm, whereas almost 4,000 had changed 1 year post surgery and after weight loss of ~10 kg/m².
Ultimately what this study shows us is that paternal weight can influence what is passed into the germline, independent of his genes. In the words of Romain Barrès, one of the study’s coauthors, “Obese men have information that can be transferred to children that could potentially affect their eating behavior. And this information can be changed if obese men lose weight. Our study doesn’t show what is transmitted to children, but it is likely that something is transmitted and it will change brain development and behavior.” That’s to say that future fathers (not just mothers) likely need to be paying attention to their weight and metabolic health. I’m hoping more research in this field comes out soon, particularly on how these messages are actually transmitted to offspring and the effect they have on children’s weight and overall metabolic health.
Image by Oliver Dodd on flickr.