miRNA signatures associated with vulnerability to food addiction in mice and humans
Alejandra García-Blanco1, Laura Domingo-Rodriguez1, Judit Cabana-Domínguez2,3,4,5
1Laboratory of Neuropharmacology-Neurophar, Department of Medicine and Life Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Abstract:
Food addiction is characterized by a loss of behavioral control over food intake and is associated with obesity and other eating disorders. The mechanisms underlying this behavioral disorder are largely unknown. We aimed to investigate the changes in miRNA expression promoted by food addiction in animals and humans and their involvement in the mechanisms underlying the behavioral hallmarks of this disorder. We found sharp similitudes between miRNA signatures in the medial prefrontal cortex (mPFC) of our animal cohort and circulating miRNA levels in our human cohort, which allowed us to identify several miRNAs of potential interest in the development of this disorder. Tough decoy (TuD) inhibition of miRNA-29c-3p in the mouse mPFC promoted persistence of the response and enhanced vulnerability to developing food addiction, whereas miRNA-665-3p inhibition promoted compulsion-like behavior and also enhanced food addiction vulnerability. In contrast, we found that miRNA-137-3p inhibition in the mPFC did not lead to the development of food addiction. Therefore, miRNA-29c-3p and miRNA-665-3p could be acting as protective factors with regard to food addiction. We believe the elucidation of these epigenetic mechanisms will lead to advances toward identifying innovative biomarkers and possible future interventions for food addiction and related disorders based on the strategies now available to modify miRNA activity and expression.
Insights
Food addiction involves loss of control over eating. MicroRNA (miRNA) signatures in the brain and blood reveal potential protective factors, like miRNA-29c-3p and miRNA-665-3p, offering new avenues for treatment.
Area of Science:
- Neuroscience
- Epigenetics
- Molecular Biology
Background:
- Food addiction is a behavioral disorder marked by impaired control over food intake, often linked to obesity and eating disorders.
- The underlying molecular mechanisms of food addiction remain poorly understood.
- MicroRNAs (miRNAs) are key epigenetic regulators implicated in various neurological and behavioral processes.
Purpose of the Study:
- To investigate miRNA expression changes associated with food addiction in both animal models and human subjects.
- To identify specific miRNAs involved in the behavioral characteristics of food addiction.
- To explore the potential of miRNAs as biomarkers and therapeutic targets for food addiction.
Main Methods:
- Comparative analysis of miRNA expression profiles in the medial prefrontal cortex (mPFC) of mice and circulating miRNAs in human cohorts.
- Functional investigation using Tough decoy (TuD) inhibition of specific miRNAs (miRNA-29c-3p, miRNA-665-3p, miRNA-137-3p) in the mouse mPFC.
- Assessment of behavioral changes related to food addiction vulnerability and compulsion-like behaviors following miRNA inhibition.
Main Results:
- Significant similarities were observed between miRNA signatures in the mouse mPFC and human circulating miRNAs, identifying key candidate miRNAs.
- Inhibition of miRNA-29c-3p in the mouse mPFC led to response persistence and increased vulnerability to food addiction.
- Inhibition of miRNA-665-3p promoted compulsion-like behavior and enhanced food addiction vulnerability, while miRNA-137-3p inhibition had no such effect.
Conclusions:
- miRNA-29c-3p and miRNA-665-3p may function as protective factors against the development of food addiction.
- These findings highlight the role of specific miRNAs in the epigenetic mechanisms underlying food addiction.
- Elucidation of these miRNA pathways could pave the way for novel biomarkers and therapeutic interventions for food addiction and related disorders.
