Study suggests paternal diet can influence propensity to obesity in offspring

Researchers at the Federal University of São Paulo conducted experiments involving rats to analyze the effects of a high-fat high-sugar parental diet. The results suggested that ingestion of hypercaloric food by male progenitors favors weight gain and a build-up of body fat in their offspring.

By Julia Moióli  |  Agência FAPESP – That a mother’s diet influences the health and metabolism of her children is a well-known fact, and women often change eating habits during pregnancy and breastfeeding. A study reported in an article published in the journal Food Research International suggests that the quality of both parents’ diet is important, potentially influencing the baby’s gut-brain axis. This connection involves biochemical signaling between the gastrointestinal tract and the central nervous system, as well as the gut microbiota, and is associated with metabolic problems such as obesity.

The study was funded by FAPESP via two projects (19/09724-8 and 17/09646-1).

Proteins and other factors relating to energy homeostasis (maintenance of a balance between energy production and expenditure), inflammatory processes and metabolic diseases in juvenile male rats were analyzed and measured. Alterations that can lead to susceptibility to disease were detected.

At the start of the experiment, the researchers induced both maternal and paternal obesity by feeding the rats a high-fat high-sugar diet (containing lard and sweetened condensed milk). Males were fed this diet for ten weeks before mating, while females received it during pregnancy and lactation. A separate group was fed a control diet.

Next, blood and tissue of male offspring were analyzed at 21 days of age (shortly after the end of the lactation period) and 90 days (the onset of adulthood). The analysis focused on the expression of protein-encoding genes in the toll-like receptor 4 (TLR4) pathway (involved in activation of the innate immune response), zonula occludens 1 (ZO1) in the colon (relating to gut permeability) and hypothalamus, orexigenic (appetite-stimulating) neuropeptides, and leptin receptor (energy homeostasis).

Blood samples were also analyzed for levels of the following: lipopolysaccharides (bacterial toxins that can cause inflammation and other health problems if they escape the gut and enter the bloodstream); ghrelin, a hormone produced mainly in the stomach that sends a signal to the brain to feel hungry; neuropeptide Y, involved in physiological processes in the central and peripheral nervous systems and one of the most potent orexigenic peptides found in the brain; and gut microbiota bacteria such as Bifidobacterium and Lactobacillus.

“In the high-fat high-sugar paternal diet group, we found significant alterations in offspring shortly after lactation, such as increased levels of lipopolysaccharides, which were positively associated with activation of inflammatory pathways in the hypothalamus [the brain region involved in appetite regulation],” said Luciana Pellegrini Pisani, last author of the article and a professor in the Department of Biosciences at the Federal University of São Paulo (UNIFESP) in Santos. “We also detected a decrease in ZO1, associated with increased gut permeability leading to higher translocation of liposaccharides [escaping the gut].”

Alterations in factors associated with energy homeostasis were also observed at both ages, including increased inflammation and adiposity, as well as weight gain associated with rising levels of neuropeptide Y and falling levels of ghrelin and GLP1, a gut hormone that stimulates insulin secretion and promotes satiety.

“The most interesting finding, however, was the alteration in adiposity and in hunger control and satiety parameters in 90-day-old offspring regardless of diet,” Pisani said. “In other words, even with a balanced diet, adiposity and energy homeostasis parameters were altered, leading to a higher probability of metabolic disease associated with obesity in adulthood.”

Induced maternal obesity resulted in higher levels of neuropeptide Y and a decrease in fecal levels of Bifidobacterium and Lactobacillus in adult offspring.

The combined effects of parental high-sugar diets were a rise in levels of neuropeptide Y at weaning and a fall in Bifidobacterium and Lactobacillus in adult offspring. These findings led to the conclusion that both parents’ diets can modulate gut bacteria in offspring and make them susceptible to metabolic disease.

Prospects

“Do these discoveries mean offspring are already condemned at birth to suffer from metabolic problems? No, although their propensity to do so is greater. These deleterious effects can be mitigated by reprogramming via lifestyle changes such as physical activity and a healthier diet, without severe restrictions or drastic increases,” Pisani said. “The study points to the possibility of planning for pregnancy and a change in the lifestyles of both the future mother and father, making a major difference to the lives of their children for generations.”

Next steps, she added, will include investigating energy homeostasis and the gut-brain connection in more depth, analyzing other tissues and including female offspring, which have already been seen to respond differently to alterations in the metabolic parameters associated with insulin resistance and inflammation.

The article “The influence of parental high-fat high-sugar diet on the gut-brain axis in male offspring” is at: www.sciencedirect.com/science/article/abs/pii/S0963996922007645?via%3Dihub.  

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