Summary: Researchers report high fat diet in female mice can have an epigenetic effect on future generations. The study found high fat diets had lead to an increased risk of obesity, insulin resistance and addictive behaviors over three generations of offspring.
Source: BioMed Central.
A high-fat diet in female mice affects their offspring’s obesity, insulin resistance and addictive-like behaviors for three generations, according to a study published in the open access journal Translational Psychiatry.
Researchers at ETH Zurich, Switzerland showed that second generation offspring – grandchildren of mice that had consumed a high-fat diet before, during and after pregnancy showed addictive-like behaviors such as increased sensitivity and preference for drugs, as well as characteristics of obesity, including changes in their metabolism. In third generation offspring (the great grandchildren), the authors observed differences between males and females, with only females showing addictive-like behaviors and only males showing obesity characteristics.
This was the case although the original female mice themselves never became obese and although none of the following generations consumed a high-fat diet.
Dr Daria Peleg-Raibstein, the corresponding author said: “Most studies so far have only looked at the second generation or followed the long-term effects of obesity and diabetes on the immediate offspring. This study is the first to look at the effects of maternal overeating up until the third generation in the context of addiction as well as obesity.”
The authors investigated these effects specifically for transmission via male offspring up until, and including, the third generation. To do so, they fed female mice either high-fat diet or a standard laboratory diet for nine weeks – pre-mating, during pregnancy and during lactation. Their male offspring were then mated with females that had been fed a standard laboratory diet to generate the second-generation offspring. The male offspring of these mice was again mated with females that had been fed a standard laboratory diet to generate the third-generation offspring.
The authors measured body weight, insulin sensitivity, metabolic rates, and blood plasma parameters such as insulin and cholesterol in second and third-generation offspring. In behavioral experiments they investigated if the mice chose a high-fat over a standard laboratory diet or an alcohol solution over water, as well as their activity levels after exposure to amphetamines. They did this to better understand if a maternal high-fat diet had an effect on obesity, overeating and drug sensitivity in subsequent generations.
Dr Peleg-Raibstein said: “To combat the current obesity epidemic, it is important to identify the underlying mechanisms and to find ways for early prevention. The research could help improve health advice and education for pregnant and breastfeeding couples and give their children, grandchildren and great-grandchildren a better chance of a healthy lifestyle. It may also provide a way of identifying risk factors for how people develop obesity and addiction and suggest early interventions for at-risk groups.”
Dr Peleg-Raibstein added: “It is quite a leap to apply conclusions from mouse studies to humans, but studying effects of maternal over-eating is almost impossible to do in people because there are so many confounding factors, such as socio-economic background, the parents’ food preferences or their existing health conditions. The mouse model allowed us to study the effects of a high-fat diet on subsequent generations without these factors.”
Further studies are needed to determine the molecular mechanism by which the effects of a female high-fat diet may be passed on to following generations.
Source: Anne Korn – BioMed Central
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Original Research: Open access research for “Transgenerational transmission of hedonic behaviors and metabolic phenotypes induced by maternal overnutrition” by Gitalee Sarker, Rebecca Berrens, Judith von Arx, Pawel Pelczar, Wolf Reik, Christian Wolfrum & Daria Peleg-Raibstein in Translational Psychiatry. Published October 2018.
Transgenerational transmission of hedonic behaviors and metabolic phenotypes induced by maternal overnutrition
Maternal overnutrition has been associated with increased susceptibility to develop obesity and neurological disorders later in life. Most epidemiological as well as experimental studies have focused on the metabolic consequences across generations following an early developmental nutritional insult. Recently, it has been shown that maternal high-fat diet (HFD) affects third-generation female body mass via the paternal lineage. We showed here that the offspring born to HFD ancestors displayed addictive-like behaviors as well as obesity and insulin resistance up to the third generation in the absence of any further exposure to HFD. These findings, implicate that the male germ line is a major player in transferring phenotypic traits. These behavioral and physiological alterations were paralleled by reduced striatal dopamine levels and increased dopamine 2 receptor density. Interestingly, by the third generation a clear gender segregation emerged, where females showed addictive-like behaviors while male HFD offspring showed an obesogenic phenotype. However, methylome profiling of F1 and F2 sperm revealed no significant difference between the offspring groups, suggesting that the sperm methylome might not be the major carrier for the transmission of the phenotypes observed in our mouse model. Together, our study for the first time demonstrates that maternal HFD insult causes sustained alterations of the mesolimbic dopaminergic system suggestive of a predisposition to develop obesity and addictive-like behaviors across multiple generations.