Acronimo: COFFEE EAT

Titolo: Role of coffee circulating metabolites in the regulation of the epicardial adipose tissue (EAT) pro-atherogenic properties: a fat-depot specific approach to reduce coronary atherosclerosis

Codice Progetto: 2022NZNZH8

Responsabile scientifico per il DMM: Prof. Francesco VISIOLI
Coordinatore: Università degli Studi di PADOVA - Prof. Francesco VISIOLI

Partner-Unità di ricerca: Consiglio Nazionale delle Ricerche - Università degli Studi "Magna Graecia" di CATANZARO - Università degli Studi di PARMA

Bando: PRIN 2022 - Decreto Direttoriale n. 104 del 02-02-2022
Durata: 28/09/2023 - 27/09/2025 (24 mesi)

Finanziamento progetto: € 276.075,00 - CUP C53D23006500006

 

Abstract del progetto

Under obesogenic conditions, the epicardial adipose tissue (EAT) undergoes a shift in the ordinary metabolic and mechanical functions towards inflammatory, dysmetabolic and pro-atherogenic phenotypes. Atherosclerotic lesions are preferentially localized in coronary artery segments surrounded by EAT. This preferential distribution of atherosclerosis associates with evidence of inflammation in EAT that eventually contributes to inflammation within and around the atherosclerotic plaques. The curb of EAT dysmetabolism and related inflammation may represent a new therapeutic target to prevent coronary atherosclerosis. Besides being the foodstuff more consumed worldwide, coffee is also the commodity most contradictorily associated with the development of CAD.

Coffee consumption is inversely correlated with cardiovascular risk, in a U-shaped manner and, although literature data support some cardiovascular benefits, there is no information on whether coffee bioactives can specifically attenuate the fat depot-specific detrimental effects and, in particular, those of increased/dysfunctional EAT. Coffee is a rich source of secondary bioactive compounds including chlorogenic acids and two kinds of alkaloids: purines as caffeine and the pyridine trigonelline. The overall objective of the present proposal is to determine whether and how coffee circulating metabolites affect the physiopathology of human EAT and whether they inhibit the EAT-related pro-atherosclerotic effects. To comprehensively tackle this aim, a network of complementary research teams with expertise ranging from the bioavailability of food bioactives to the application of nutrigenomic, physiopathology and computational knowledge has been constituted. The properties of selected coffee circulating metabolites will be directly tested and characterized in cultures of human EAT and monocytes samples collected from CAD patients and in cell cultures of adipocytes and monocytes. The project will be implemented through 4 work packages devoted to: determine in EAT organ culture and cultured adipocytes the modulation exerted by coffee in terms of cellular bioactive coffee uptake, regulation of inflammation, lipid and glucose metabolism and mitochondrial dysfunction; determine coffee effects on the pro-atherogenic activities of EAT in in vitro models of early atherogenesis. The understanding of dysfunctional features of EAT and their relationship with CAD may pave the way to new dietary strategies and food supplements able to alleviate the proatherogenic traits of EAT, thus restoring adipose tissue homeostasis, its endocrine/paracrine action and influences on adjacent coronary arteries. This will have considerable positive scientific and economic impacts, foreseeing the possibility to improve patient stratification risk and the related nutrigenomic response and the opportunity to use tailored nutritional coaching and agri-food co-products as validated supportive tools in cardiovascular managements.