**3. Ectopic fat depots and CVD risk**

## **3.1 Ectopic fat depots**

Although the major known ectopic fat depot is the hepatic depot, there are other abnormal fat depots that contribute to the development of cardiovascular diseases. Some of these are: pericardial and epicardial depots despite being used many times in an undifferentiated way, they have a different anatomical locations and their relationship with cardiovascular diseases is different. The pericardial depot is located at the level of the pericardial sac and has been related to a high BMI, traditional cardiovascular risk (CVR) risk factors, and elevated atherogenic cholesterol. Additionally, the amount of pericardial fat has been associated with an increased risk of coronary heart disease, atherosclerosis, and heart failure adjusting for age, sex, BMI, and abdominal circumference; but not adjusting for traditional CVR factor and either when adjusting for levels of more atherogenic cholesterol particles [6].

VAT on the other hand represents the visceral fat contained between the external myocardium wall and the visceral lamina of the pericardium. It has been associated with a general CVR score and arterial stiffness in patients with CVD and DM2 [7].

Reports from multiple studies presented a high association between the pericardial depots and CVD. For example, a study of atherosclerosis showed the pericardial fat and a higher risk of all CVD causes, hard atherosclerotic CVD, and HF but not intrathoracic fat [8]. Another study that analyzed all-cause mortality risk after adjustment for age, sex, lifestyle variables, lipids, glucose, and adipocytokines was higher by increment in pericardial fat, but it did not proof enough information to predict the events of CVD beyond traditional risk factors [9].

Epicardial adipose tissue (EAT) is the visceral fat layer located around the heart and is believed to be important for the buffering of the coronary arteries and in providing fatty acids as a source of energy for the cardiac muscle. Reviews have shown that this deposit may be considered highly insulin resistant and also indicator of cardiovascular risk because of the secretion of pro-inflammatory cytokines and carotid artery stiffness. In addition, this can produce sleep apnea severity in woman independently of BMI, and this last one is associated with higher CVD risk [10, 11].

Currently, the way to reduce the announced ectopic fat (adipose tissue depots) has been investigated. There are a lot of nonpharmacological strategies to be applied based on lifestyle interventions, some authors dare to say could be more effective than pharmacological therapies. One of those strategies are exercises such as aerobic in nature, which may reduce VAT unchanged on weight loss; and reports of losing VAT by only resistance and high-intensity raining are equivocal [12, 13]. Thus, exercise interventions not just can decrease the VAT, apparently have impact in reducing hepatic, epicardial, and pericardial fat. However, there is not enough information to support a significant reduction in epicardial fat with exercise as the caloric restriction strategy to reduce it [14].

The recommendation for physical activity of 150 min per week may be sufficient to reduce VAT with no further reduction with additional activity. It is very important to highlight that exercise can reduce VAT even in the absence of weight loss [15].

According to data from the National Health and Nutrition Examination Survey, central obesity has higher risk of cardiovascular mortality compared with patients with the same BMI but without central adiposity. This has been called normal weight central obesity and expected survival estimates were consistently lower for those with central obesity when controlled for age and BMI [16, 17].
