The present study aimed to clarify the relation of different central and peripheral adipose tissue measures to the presence of the MS and related cardiometabolic risk factors in a large sample of essentially healthy adults. VAT mass was a strong independent predictor of the MS in men and women, even after adjustment for ASAT and BMI as well as age, smoking status, FFM, and physical activity level. This finding is consistent with previous reports, which have found that VAT is a stronger predictor of the MS and its component risk factors than is ASAT (16
). It also is consistent with the extensive literature showing that VAT is more lipolytically active and less responsive to the adipogenic effects of insulin and that it produces a number of adipokines (eg, adiponectin, plasminogen activator inhibitor-1, and interleukin-6) in greater concentration than does SAT (7
We hypothesized that greater ASAT mass, LEG fat mass, and triceps skinfold thickness may have protective effects (ie, may be associated with lower odds of theMS) in this sample of healthy adults. Goodpaster et al (16
) showed in the Health, Aging, and Body Composition Study that older adults with the MS tend to have lower percentage body fat than those without the MS. In the present study, a significant interaction between VAT mass and subcutaneous adiposity traits was found in men: elevated ASAT mass and peripheral subcutaneous fat measures were deleterious when VAT mass was low, but they became more protective against the MS (ie, they reduced the OR) as VAT mass increased. There were relatively few subjects with discordant values on these measures [eg, only 4% of men were in the top tertile for VAT mass (>4.2 kg) and the bottom tertile for ASAT mass (<2.2 kg)]. The relative rarity of such subjects most likely led to the relatively wide CIs of our probability estimates at the tails of the distribution of VAT, and it may explain why smaller studies have not identified this protective effect at all. Nonetheless, our conclusions are based primarily on the significance of the interaction term in the continuous-variable models, and neither the figures nor the tables show estimates that extended past actually observed data points. Our finding is consistent with the paradigm of ectopic fat accumulation, in which increased metabolic risk stems from exceeding the capacity of the subcutaneous adipocytes to differentiate and accommodate excess circulating lipids, which results in ectopic deposition of lipids—that is, deposition in the liver, muscles, pericardium, and visceral compartments (1
); this outcome was reviewed by Bays et al (39
). The present study is, to our knowledge, the first to suggest that elevated abdominal SAT mass, as well as peripheral or extremity SAT, may have protective effects in the presence of high VAT.
Kuk et al (23
) found that, whereas VAT area was a significant predictor of the MS at all 8 measurement locations they examined, the odds were twice as high for VAT area measured in the upper abdomen [near L1–L2 (unadjusted OR = 8.8)] than for VAT area measured at L4–L5 (unadjusted OR: 3.9; confidence limits not provided), which indicates that the single MRI or computed tomography image chosen for analysis could affect the perceived severity of risk associated with elevated VAT. Shen et al (27
) reported that the L4–L5 image never had the highest correlation with MS risk factors and often had a significantly lower correlation than did total VAT volume or images located superior to L4–L5. They suggested choosing a single image 10–15 cm above L4–L5 in men and either 5 cm above or 5 cm below L4–L5 in women. In the present study, the wide CIs around the estimates precluded our choosing any one particular image as statistically superior to the others, but the highest risk was associated with midabdominal images (near L2–L3 in men and near L3–L4 in women), rather than with lower abdominal images (near L4–L5). By looking at individual risk factors, we identified a set of contiguous images containing the statistically equivalent, highest correlations with risk factor levels for each sex, and these ranges included the L4–L5 image ≈50% of the time. In contrast, images located 4–8 cm above L4–L5 provided correlations that were consistently high in magnitude for every risk factor examined (other than LDL), in both men and women. Therefore, we would recommend that, if a small number of images are to be analyzed, an image located in that region [which we have found to lie close to the L2–L3 intervertebral space (35
)], rather than the L4–L5 image, would best capture the relation between VAT and cardiometabolic risk factors in both sexes.
Related to this finding is the documented metabolic heterogeneity within the VAT depot itself; upper abdominal VAT primarily comprises the highly lipolytic mesenteric and omental adipose tissues, which are drained by the portal vein, whereas lower abdominal VAT has a greater proportion of retroperitoneal adipose tissue, which is drained nonportally (40
). Given these differences, it is possible that not only the amount but also the spatial distribution of VAT within the abdomen has consequences for cardiometabolic risk. Novel findings from the present study are that persons vary greatly in the patterning of VAT (represented in the present analysis by the anatomical location of the maximum VAT area for each subject), that the location of the maximum VAT area tends to move upward (ie, cranially) in the abdomen with increasing age and adiposity, and that LDL-cholesterol concentrations are related to VAT patterning in men and women, independent of age and adiposity. However, the lack of an effect of VAT patterning on the odds of the MS and other risk factors indicates the need for further analysis and replication from studies with multiple-image VAT data.
A limitation of the present study is that risk factor data were available only for non-Hispanic whites; the same relations between VAT and disease risk factors may not apply in other racial-ethnic groups. Furthermore, the subjects were essentially a convenience sample including all nondiabetic subjects in 3 ongoing studies of body composition and CVD risk factors in the greater Dayton area. It is possible that the nonrandom nature of the sampling design (ie, it was restricted to relatively healthy volunteers) may have biased the relations between different adiposity measures and cardiometabolic risk. However, our results are similar to those of other studies documenting the greater risk associated with VAT than with SAT, as well as the effects of image location on cardiometabolic risk factor levels (23
). In addition, we adjusted for important possible confounders of the disease risk–body composition relation, including physical activity level and cigarette smoking.
In conclusion, although VAT mass was a stronger predictor of the MS than was ASAT, elevated ASAT mass (and other subcutaneous fat measures) were found to protect against the MS in men with high VAT mass, as predicted by the ectopic fat paradigm. Our findings also indicate that the L4–L5 intervertebral space is not optimal for detecting the relation of VAT to disease risk. Rather, an image located 4–8 cm cranially from L4–L5 would more strongly and consistently correlate with cardiometabolic risk factor levels. Finally, we identified a novel aspect of abdominal adiposity—the spatial patterning or topography of VAT—that appears to stem primarily from differences in age and the amount of visceral fat, but that had independent effects on LDL-cholesterol concentrations. Further work is needed to identify the genetic and environmental determinants of ectopic fat deposition and VAT patterning.