Author + information
- Robert J. Gropler, MD⁎ ( and )
- Linda R. Peterson, MD
- ↵⁎Reprint requests and correspondence:
Dr. Robert J. Gropler, Cardiovascular Imaging Laboratory, Campus Box 8225, Edward Mallinckrodt Institute of Radiology, 510 South Kingshighway Boulevard, St. Louis, Missouri 63110
The metabolic syndrome is a vexing problem for the cardiologist, internist, and endocrinologist. It is a constellation of peripheral signs that indicate insulin resistance in patients but does not quantify it. The metabolic syndrome helps the physician to identify patients who are at increased risk of cardiovascular disease (CVD) with a simple physical examination and standard laboratory findings. Indeed, the presence of the metabolic syndrome reminds us that the cardiovascular system is part of an integrated whole, and as such, is affected by disease processes that involve other key tissues and organs. However, exactly how the metabolic syndrome confers this increased risk of CVD is poorly understood. For example, the relative importance in conferring increased CVD risk of each component is unknown. In this regard, it is especially nebulous how increased abdominal girth, one of the hallmarks of the metabolic syndrome, increases CVD risk. For example, increased abdominal girth is associated with insulin resistance and diabetes mellitus, both of which increase CVD risk. Moreover, it occurs typically with obesity, another known risk factor for CVD. Consequently, the unique biological attributes of increased abdominal girth that contribute to increased CVD risk are unclear.
The first imaging studies that evaluated how increased abdominal girth may relate to increased CVD risk demonstrated that it was visceral adipose tissue (VAT) burden, as opposed to the burden of subcutaneous abdominal tissue (SAT), that was most closely associated with CVD risk. Both computed tomography and cardiac magnetic resonance imaging have been used to quantify the volume of VAT and SAT (1). However, current dedicated computed tomographic and cardiac magnetic resonance imaging techniques are limited to measuring the structure, not in vivo metabolism, of these adipose depots. The study by Christen et al. (2) in this issue of iJACC moves beyond these techniques, using 18F-fluorodeoxyglucose and positron emission tomography (PET) to measure the glucose metabolism of the different fat depots, which are colocalized with adipose structures using combined PET/computed tomography. This technique for determining the 18F-fluorodeoxyglucose uptake activity of adipose tissue at different depots (i.e., VAT vs. SAT) is depicted in Figure 1 of that article. Although colocalization with PET/computed tomography is used extensively in oncology, its application for the evaluation of adipose tissue is new.
As expected, the authors found that VAT, which is often described as metabolically active, had a higher glucose uptake than SAT. However, there were no differences between the glucose uptake by lean subjects' VAT and the obese subjects' VAT. Because an increased amount of VAT is associated with increased inflammation, infiltration, and activation of tissue macrophages; hypertrophied metabolically active fat cells; and an adverse adipokine profile (e.g., less adiponectin, more leptin) (3), one might have expected the VAT in obese subjects to have greater glucose uptake than that in lean subjects. However, this finding is similar to that of another study, which suggested that total glucose uptake by VAT is not different in normal controls compared with that in obese subjects with and without diabetes mellitus (4). Because the amount of VAT is expected to be less in the lean than the obese, this suggests that the VAT of lean subjects has a higher glucose uptake per kilogram, a finding that been observed by others (4). Moreover, as pointed out by the authors, it is likely that VAT in obese subjects exhibits lower glucose uptake per kilogram due to insulin-resistant adipocytes.
Christen et al. (2) not only imaged the glucose uptake from the adipose depots from different locations, but they also determined from laboratory studies that the stromal vascular cells from VAT take up more glucose than stromal vascular cells from SAT (at baseline and after stimulation with tumor necrosis factor + interleukin-1β). Unfortunately, they did not also evaluate the in vitro glucose uptake of the adipocytes of the VAT and SAT as well. Nevertheless, it appears that some of the increased glucose metabolic activity of VAT is due to the company that its adipocytes are keeping as opposed to the adipocytes themselves.
Thus, this article moves our understanding beyond the initial findings that 1) not all adipose tissue is alike and 2) adipocytes can make and respond to hormones and cytokines to realizing that adipose tissue is a complex environment composed of varying amounts of many different types of cells including the stromal vascular cell fraction (which includes inflammatory cells, mesenchymal stem cells, T-regulatory cells, endothelial and adipocyte precursors) (5). Recent studies have also demonstrated that the extracellular matrix also influences adipose activity and inflammation (6). All these types of cells and extracellular matrix are influencing one another's activity, and the sum of their activity is the activity of the tissue as a whole.
From an imaging perspective, the implications of these findings are manifold. They highlight the potential of imaging techniques such as those described in this study to delineate how biological events remote from the cardiovascular system may influence disease involving this system. These findings also underscore the limitations of more generalized biological imaging techniques such as the measurement of glucose uptake to specifically identify and localize the key biological events in VAT that may influence the development and progression of CVD. As a consequence, they emphasize the need for the development of molecular imaging approaches that noninvasively target specific cell types and/or biological processes that comprise VAT and contribute to CVD.
↵⁎ Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
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