Paternal over-nutrition may lead to generational obesity and metabolic dysfunction

Paternal intake of a high-fat diet (HFD) can cause genetic changes that lead to generational obesity and metabolic dysfunction—including body weight and fat mass increases and changes in blood pressure, triglyceride levels and fat metabolism—in mice, according to Japanese researchers at Okayama University. The effects of paternal over-nutrition were significantly improved when offspring were fed a control diet lower in fat. Exposure to a control diet for two generations completely erased the metabolic effects caused by grandpaternal high-fat diet consumption.

Previous studies have found that maternal obesity may play a role in transmitting obesity- and diabetes-causing traits across generations. Studies in humans have also associated body mass index of the mother and father with that of young and grown children. "We examined whether paternal obesity induced by high-fat diet exposure affected the metabolic status of offspring through epigenetic changes to the adiponectin and leptin genes," the researchers wrote. "Furthermore, we investigated whether a normal diet for multiple generations abolished such epigenetic changes after paternal HFD exposure before conception."

The researchers found that while a mother's high-fat diet during pregnancy had a greater impact on obesity and metabolic changes in offspring, a father's consumption of a high-fat diet compounded these effects. The changes occurred in both male and female offspring.

The research team also saw a difference in the number of generations it took to correct the metabolic changes caused by high-fat diet intake by mothers and fathers. When offspring of the high-fat diet-fed males were given a control diet, the metabolic effects of the high-fat diet exposure were diminished. When the next generation was given a control diet, the metabolic effects were completely abolished. However, when mothers consumed a high-fat diet during pregnancy, it took three generations of control diet feeding (through the great-grand generation) to erase the effects of that exposure.

The cause of the metabolic changes that occur following paternal over-nutrition and the reversal of these effects after control diet feeding in subsequent generations is unclear. Environmental factors that affect the development of the first-generation fetus may directly affect its developing germ cells (which will become the next generation) or the fetus could transfer genetic changes that it experiences into its germ cells.

"Understanding how epigenetic mechanisms contribute to the transgenerational transmission of obesity and metabolic dysfunction through paternal and maternal lineages is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome," the researchers wrote.


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