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Effects of a high-fat diet may be passed on for three generations

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.

-ENDS-

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Notes to editor:
1.    Research article:
Transgenerational transmission of hedonic behaviors and metabolic phenotypes induced by maternal overnutrition
Translational Psychiatry 2018
DOI: 10.1038/s41398-018-0243-2

The article is available at the journal website.
 
Please name the journal in any story you write. If you are writing for the web, please link to the article. All articles are available free of charge, according to BMC's open access policy.

2.    Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod's discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.

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