When a female mouse is fed a high-fat diet her children, grandchildren and great grandchildren have a greater risk of obesity and addiction — because of changes to the brain reward system.
Diet can mess with the brain. Animal studies have shown that the offspring of mothers consuming a high-fat diet have a less sensitive reward system: they need to consume more food or pleasure-enhancing drugs to feel full or satisfied. Therefore, these individuals are more likely to become obese and addicted to drugs.
Daria Peleg-Raibstein at the Swiss Federal Institute of Technology and her colleagues were interested in the effect of a high-fat diet on the second and third generation — grandchildren and great grandchildren. The team fed female mice with a high-fat diet for nine weeks: three weeks before they mated, and another six weeks through the subsequent pregnancy and lactation period. These mice did not become obese during the nine-week period.
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All offspring were offered a normal diet. Then, the males were mated with healthy females that had been born to “normal diet” mothers to produce a second generation of offspring. Finally, males from this second generation were mated with females from “normal diet” families to produce a third generation.
Alcohol preference
The team found that the second- and third-generation mice had a 7 per cent greater body weight than expected for the diet they had been offered. They also had a greater than anticipated preference for drinking alcohol.
By analysing the mice brains, Peleg-Raibstein and her colleagues found those belonging to mice with high-fat diet ancestors had reduced dopamine levels — by as much as 50 per cent —and a larger number of dopamine receptors. Dopamine is the brain’s signal for pleasure. Both brain changes might have increased the amount of food and alcohol the mice needed to consume to feel satisfied.
“This study is the first to look at the differing effects of maternal overeating up until the third generation,” says Peleg-Raibstein. “But the mechanism of how the changes in the brain reward system was transmitted across generations is not yet clear.”
żěè¶ĚĘÓƵs suspect that a high-fat diet could alter dopamine-related gene expression by adding or removing a methyl group from the DNA, a process called transgenerational epigenetics. But Peleg-Raibstein didn’t find a significant change in offspring’s DNA methylation. She thinks other pathways may have been involved.
Peleg-Raibstein also points out that it’s too early to say whether there are implications for our family histories. “Because this is a mouse study, we need to be careful about drawing conclusions for humans,” she says.
Translational Psychiatry
