Deciphering the role of adipose tissue in cardiac health and disease: ADIPOhealth

Obesity is a major risk factor for cardiovascular diseases (CVD), primarily due to its disruption of heart metabolism and the alteration of crucial signaling pathways involved in maintaining cardiac function, including those regulating energy homeostasis, myocardial contractility, and stress response. Nevertheless, the underlying mechanisms for these effects remain poorly understood. Obesity leads to changes in the secretion, by adipose tissue (AT), of metabokines—proteins, peptides, metabolites, and extracellular vesicles (EVs)—that are critical for inter-organ communication and significantly affect heart function.AT is a key endocrine organ involved in whole-body homeostasis, yet its impact on cardiac health is still not fully understood. We hypothesize that AT dysfunction is a key driver of heart disease through disrupted metabokine secretion. Our preliminary findings suggest that specific AT alterations profoundly affect heart metabolism and function. ADIPOhealth aims to advance our understanding of how AT controls cardiac function through the following objectives:1.Identify novel metabokines (adipokines, metabolites, microproteins, microRNAs, and EVs) secreted by AT that contribute to the development of heart disease.2.Discover novel metabokines that regulate cardiomyocyte metabolism using cellular models.3.Investigate, in mouse models of AT-specific dysfunction, how cardiac function may be influenced by changes in metabokines.4.Functionally characterize these metabokines in cell culture, mouse models, and human samples.5.Develop therapeutic strategies targeting AT dysfunction and metabokine-induced cardiac damage.By integrating multi-omics data from human and mouse studies, we aim to elucidate the molecular mechanisms by which AT influences heart health. Our results not only will deepen our understanding of metabolic crosstalk between organs but will also identify new therapeutic targets to combat cardiometabolic diseases (CMDs).