miRNA signatures associated with vulnerability to food addiction in mice and humans

Alejandra García-Blanco; Laura Domingo-Rodriguez; Judit Cabana-Domínguez; Noèlia Fernández-Castillo; Laura Pineda-Cirera; Jordi Mayneris-Perxachs; Aurelijus Burokas; Jose Espinosa-Carrasco; Silvia Arboleya; Jessica Latorre; Catherine Stanton; Bru Cormand; Jose-Manuel Fernández-Real; Elena Martín-García; Rafael Maldonado

doi:10.1172/JCI156281

miRNA signatures associated with vulnerability to food addiction in mice and humans

J Clin Invest. 2022 May 16;132(10):e156281. doi: 10.1172/JCI156281.

Authors

Alejandra García-Blanco¹, Laura Domingo-Rodriguez¹, Judit Cabana-Domínguez^{2

3

4

5}, Noèlia Fernández-Castillo^{2

3

4

5}, Laura Pineda-Cirera^{2

3

4

5}, Jordi Mayneris-Perxachs^{6

7

8}, Aurelijus Burokas^{1

9}, Jose Espinosa-Carrasco¹⁰, Silvia Arboleya^{11

12}, Jessica Latorre^{6

7

8}, Catherine Stanton^{11

12}, Bru Cormand^{2

3

4

5}, Jose-Manuel Fernández-Real^{6

7

8

13}, Elena Martín-García^{1

14}, Rafael Maldonado^{1

14}

Affiliations

¹ Laboratory of Neuropharmacology-Neurophar, Department of Medicine and Life Sciences, Universitat Pompeu Fabra (UPF), Barcelona, Spain.
² Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain.
³ Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
⁴ Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain.
⁵ Institut de Recerca Sant Joan de Déu (IR-SJD), Esplugues de Llobregat, Barcelona, Catalonia, Spain.
⁶ Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), Girona, Spain.
⁷ CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Girona, Spain.
⁸ Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain.
⁹ Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
¹⁰ Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain.
¹¹ APC Microbiome Institute, University College Cork, Cork, Ireland.
¹² Teagasc Food Research Centre, Moorepark, Fermoy, Ireland.
¹³ Deparment of Medical Sciences, Faculty of Medicine, University of Girona, Girona, Spain.
¹⁴ Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, 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.

Keywords: Addiction; Epigenetics; Neuroscience.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Food Addiction* / genetics
Humans
Mice
MicroRNAs* / metabolism
Prefrontal Cortex / metabolism

Substances

MIRN137 microRNA, mouse
MicroRNAs

Grants and funding

This work was supported by the Spanish ‘Minsterio de Ciencia e Innovación – MICIN, ‘Agencia Estatal de Investigación – AEI’ (#PID2020-120029GB-I00/MICIN/AEI/10.13039/501100011033, RD21/0009/0019 to R.M, #SAF2015-68341-R to B.C., #SAF2017-84060-R-AEI/FEDER-UE to L.D., #RTI2018-100968-B-100 to N.F.-C.), the ‘Generalitat de Catalunya, AGAUR’ (#2017 SGR-669 to R.M., #2017 SGR-734 to J.M.F.R., #2017-SGR-738 to B.C), ‘ICREA-Acadèmia’ (#2020 to R.M. and #2022 to J.M.F.R.), “European Commission-DG Research” (PainFact, #H2020-SC1-2019-2-RTD-848099, QSPain Relief, #H2020-SC1-2019-2-RTD-848068 to R.M., CoCA, #H2020-667302, MiND, #H2020-643051 and Eat2beNICE, #H2020-728018 to B.C. ‘ the Spanish ‘Instituto de Salud Carlos III, RETICS-RTA’ (#RD16/0017/0020 to R.M., FIS PI15/01934, PI18/01022, PI21/01361 to J.M.F.R), the Spanish ‘Ministerio de Sanidad, Servicios Sociales e Igualdad, ´Plan Nacional Sobre Drogas’ (#PNSD- 2021I076 to R.M., #PNSD-2017I050 to E.M.-G., #PNSD-2017I050 to B.C., #PNSD-2020I042 to N.F.-C.), ‘Fundació La Marató-TV3’ (#2016/20-30) to E.M.-G., and the European Regional Development Fund (project No. 01.2.2-LMT-K-718-03-0099) under grant agreement with the Research Council of Lithuania (LMTLT) to AB, and the Project ThinkGut (EFA345/19) 65% co-financed by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra programme (POCTEFA 2014-2020).