How does fat cause heart diseases? Effects of epicardial adipocytes on cardiomyocyte signalling and contractility

Masoud, Said; Bootman, Martin D.; McDonald, Fraser; MacQueen, Hilary and Rietdorf, Katja (2016). How does fat cause heart diseases? Effects of epicardial adipocytes on cardiomyocyte signalling and contractility. In: 14th International Meeting of the European Calcium Society, 25-29 Sep 2016, Valladolid, Spain.


The heart is surrounded by a layer of fat known as epicardial adipose tissue (EAT). EAT thickness is a predictor for several cardiac diseases. Adipocytes within the EAT cause harmful effects via secretion of adipokines and cytokines, which can act on neighbouring cardiomyocytes in a paracrine manner. However, EAT also has beneficial effects, and is critical to the heart’s function by providing energy and offering physical protection. We found that adipocytes caused negative chronotropic (0.51 ± 0.01 vs. 0.32 ± 0.04 Hz contraction frequency) and negative inotropic responses (6.9 ± 0.3 vs. 3.8 ± 0.5 μm contraction amplitude) after 3 days of co-culture with neonatal rat ventricular cardiomyocytes. Using signalling arrays we found a significant up-regulation of cardiomyocyte pro-apoptic signalling pathways by the adipocytokines TNF-α and Activin A. In contrast, adiponectin reduced ERK and mTOR activity, in line with its proposed cardioprotective effects. These data illustrate that adiposederived adipocytokines have complex effects on both contractility and signaling pathways in cardiomyocytes. Because mature adipocytes do not attach to cell culture surfaces it is impossible to study the paracrine interaction between adipocytes and cardiomyocytes for prolonged periods using conventional 2-dimensional co-cultures. Addition of adipocyte-conditioned medium is often used, but cannot replicate the paracrine interactions occurring between cells being in physical contact. To study the effects of adipocytes on adjacent cardiomyocytes, and vice versa, over prolonged periods of time we are establishing a 3-dimensional co-culture. This approach allows cellular phenotypes, calcium signalling and contraction to be measured within the cultures.

Viewing alternatives

No digital document available to download for this item

Item Actions