ReviewEctopic fat and cardiometabolic and vascular risk
Introduction
During the last decade, substantial progress has been made toward the elucidation of the pathophysiological associations between obesity and cardiometabolic diseases, including hypertension, dyslipidemia, glucose intolerance and cardiovascular disease [1].
The observation that body fat distribution, metabolic profiles, and the degree of association of these parameters with cardiovascular risk vary widely in individuals with obesity or even normal weight has been a key insight into this issue. Current data suggest that fat distribution might be a better predictor of cardiovascular disease than obesity itself [2], [3]. Body shape and how regional adipose tissue handles and stores excess dietary energy have substantial cardiometabolic implications [4], [5].
These findings have led to the hypothesis that accumulation of fat in specific locations or as ectopic fat may partially contribute to the association of adiposity with cardiometabolic risk (Fig. 1). In particular, fat accumulation in the abdominal visceral area has an important role in the development of cardiometabolic risk [6]. Fat stores in the liver and muscle are associated with insulin resistance and adverse metabolic phenotypes, independent of total adiposity [7], [8]. More recently, fat depots with primarily locally acting effects have been studied. For example, pericardial fat is associated with coronary atherosclerosis, even after accounting for abdominal fat [9]. These data support the concept that pericardial fat might have a harmful perivascular effect on the coronary arteries.
In contrast, fat depots in certain areas may be protective in terms of metabolic risk. In particular, the propensity to deposit fat in the gluteofemoral region may be associated with lower cardiometabolic risk [10]. Thus, regional fat distribution, in addition to overall fat volume, may be important in understanding the link between obesity and cardiometabolic risk. In this article, we introduce the imaging techniques used to characterize ectopic fat depots and review the literature investigating the clinical correlations and implications of ectopic fat accumulation from a cardiometabolic and vascular disease perspective. Conceptually, we consider fat depots as either those that act primarily systemically, such as abdominal visceral fat or intrahepatic fat, or those that act primarily locally, such as pericardial fat. Finally, we suggest future study directions in this area of research.
Section snippets
Imaging techniques for assessing ectopic fat depots
Various imaging techniques can be used to measure tissue composition, particularly fat, in major organs or in different compartments of the human body (Table 1 and Fig. 2).
Systemically acting ectopic fat depots
Ectopic fat depots that are particularly large (such as VAT) or that occur in organs that have central functions in metabolism (such as the liver) are considered to be primarily systemically acting fat depots [43], [44]. These fat depots are associated with systemic surrogate markers of inflammation and insulin resistance, as well as with clinical outcomes, such as type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and stroke (Fig. 1) [1], [2], [3].
Locally acting fat depots
Locally acting fat depots are those that have effects primarily in adjacent anatomic organs. The endocrine and paracrine actions of adipocytes, especially of those neighboring cardiovascular organs, are most likely to link obesity and cardiovascular disease [117]. Locally acting fat depots may be associated with unfavorable effects on adjacent organs, directly via lipotoxicity and indirectly via the secretion of adipokines and other cytokines [118]. In particular, fat located around components
Summary
This article has described the various imaging techniques used to characterize ectopic fat depots. Representative cohort studies which assessed various adipose tissues and investigated its clinical implication are shown in Table 2. Advanced CT techniques have been used increasingly to measure ectopic fat to determine local or systemic effects on metabolic and cardiovascular risk; however, a radiation hazard is still associated with this technique. MRI is a powerful tool for assessing body
Conclusions and future directions
The deleterious effects of excess adiposity have great clinical importance. Although the reduction of whole-body fat would be ideal among individuals who have obesity, the additional benefit of targeting fat depots at specific locations in individuals at greater cardiometabolic risk represents an alternative approach.
A recent meta-analysis based on 58 cohorts has demonstrated that BMI, waist circumference, and waist-to-hip ratio (assessed singly or in combination) do not improve cardiovascular
Disclosures
The authors declare no conflict of interest.
Acknowledgment
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. James B. Meigs is supported by 2K24 DK080140.
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