Epigenetics May Explain Vulnerability to Food Addiction

Scientists find microRNA signatures in the brain linked to compulsive eating disorder

Food is a necessity as much as it is a pleasure to pretty much everyone. But to the food addict, food is more like a drug, providing an overload of feel-good chemicals to the brain, increasing appetite and consumption tolerance. As a result, most food addicts suffer from health problems like obesity, eating disorders, and malnutrition. 

Because food cannot be abstained from during recovery, people who struggle with this disorder find it challenging to overcome, especially when unhealthy fast food is cheap and readily available. Moreover, addicted behavior such as overeating tends to run in families partly due to exposure to certain foods, learned behaviors, and genetic susceptibility.

With the prevalence of obesity with comorbid binge eating on the rise worldwide, researchers are seeking new ways to understand this disorder better. Currently, not much is known about the underlying neurobiological substrates involved in food addiction. However, previous studies have found that other types of addicted behavior disorders share similar biological mechanisms. 

Researchers from Spain’s Universitat Pompeu Fabra (UPF) in Barcelona are now contributing to the understanding of food addiction with their latest study examining the epigenetic signatures in the brain related to addiction. Specifically, they focused on microRNAs, an epigenetic modulator of gene expression, in the medial prefrontal cortex (mPFC), a region in the brain linked to loss of control for intaking food.

“Having identified the mechanism, we ask ourselves why some individuals are resilient while others are addicted. To do so, we focus on epigenetic factors, that is, external or environmental factors that modify gene expression,” said Elena Martin from the Neuropharmacology-Neurophar research group at UPF, who co-led the study with Rafael Maldonado.

Epigenetics, which is involved in the interplay between genes and the environment, seems crucial in the susceptibility towards developing food addiction. DNA methylation, histone modifications, and microRNAs are epigenetic mechanisms that affect gene expression without altering the DNA sequence. 

Previous studies have shown that microRNAs play an essential role in metabolic changes leading to obesity. These changes are also found in several psychiatric disorders and the physio-pathological processes linked to drug addiction, including synaptic plasticity, reward, withdrawal, and relapse. 

In the current study, the researchers used highly food addicted and non-addicted populations of mice to identify differentially expressed microRNAs in the mPFC linked to food addiction. They also tested the circulating microRNAs from a group of healthy volunteers and used the Yale Food Addiction Scale (YFAS) 2.0 questionnaire to determine the degree of high-fat/ high-sugar substance dependence.

“The most fascinating finding was that the same microRNAs that were affected in the mouse brain were also altered in people’s plasma,” explains UPV researcher José Manuel Fernández-Real. “Intriguingly, the same microRNAs were associated with the degree of food addiction quantified by means of this questionnaire.”

The results showed that the primary microRNAs associated with food addiction are also involved in carbohydrate and lipid digestion, changes in brain structure, insulin resistance, as well as other types of substance abuse. In addition, the two main components of behavioral alteration seen here were high motivation to obtain food and compulsive searching for food despite the negative outcomes\es, 

“Interestingly, we have seen that two specific epigenetic changes appear to be responsible for these behavioral hallmarks of the disease. The similarities between mouse and human outcomes give significant translational value to the study,” said Rafael Maldonado.

The team believes their study will lead to new approaches for identifying potential biomarkers that can predict the early diagnosis of this disease. Their findings could also help develop new therapies to treat food addiction and other eating disorders using presently available methods to modify microRNA activity or expression.

Source: A. García-Blanco, et al. miRNA signatures associated with vulnerability to food addiction in mice and humans. Journal of Clinical Investigation, 2022; 132 (10).

Reference: Researchers identify key epigenetic markers in vulnerability to developing food addiction. Universitat Pompeu Fabra – Barcelona, May 9, 2022.

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