‘Involvement of the Fgf21 System in Obesity-Related Heart Disease’

Marta Giralt Oms, María del Rosario Iglesias Coll, Ana Planavila Porta, Ibon Redondo Angulo and José Miguel Gallego Escuredo, University of Barcelona.

Obesity is one of the increasing risk factors in our societies with a greater impact on the development of cardiac disease. In addition to coronary disease, hypertension and other associated phenomena, obesity exerts direct harmful effects on the heart through mechanisms not yet well known. In recent years the hormonal factor FGF21 has emerged as a key regulator of metabolism, with important effects protecting against the metabolic disorders associated with obesity effects.

Recently, our laboratory has found beneficial effects of FGF21 directly on the heart, particularly to promote the prevention of experimentally-induced cardiac hypertrophy. The main objective of this project is to determine whether FGF21 plays a key role in the metabolism / heart function as a direct factor for heart protection in the cardiomyopathy associated with obesity, not attributable to coronary dysfunction or hypertension.

For this purpose the experimental mouse model of obesity by overfeeding with high fat diet were used. We will determine how the FGF21 system (systemic and specific in the heart) is affected in relation to induced cardiac disorders (cardiac hypertrophy, functional alterations, induction of cardiac inflammatory and metabolic dysregulation).

It will establish whether the lack of a functional FGF21 system (FGF21 “knockout” mice) exacerbates the deleterious effects of obesity on cardiac function induced in the previous model. We will also determine whether treatment with FGF21 (through specific overexpression of FGF21 in heart using adeno-associated virus, AAV.9-FGF21) restores / protects the cardiac function altered by obesity.

Finally, we will establish whether the observed effects (cardiac protection) are reproducible in a cellular system (cardiomyocytes) and whether FGF21 protects against pro-inflammatory and metabolic dysfunction elicited by fatty acids (palmitate).