Consistent with our hypotheses, IAAT was independently and positively related to worsening of blood lipids and Si
, whereas both leg fat and aerobic fitness were independently and positively related to improved blood lipids and Si
. Previous studies have shown similar relationships for IAAT and leg fat (9
). However, to our knowledge, this is the first study to show these results to be independent of age and aerobic fitness in a mixed group of AA and EA women. Although not the focus of the study, it is interesting to note that age was not related to worsening of the blood lipid profile after adjusting for fat distribution and aerobic fitness. In fact, the significant negative adjusted β for age and fasting insulin, and significant positive adjusted β for age and Si
suggested less risk for type 2 diabetes with increasing age if IAAT is kept low and aerobic fitness is kept high. The women in this study were relatively homogeneous for body composition, being neither obese nor lean. In addition, none of the women were diabetic and few had an abnormal blood lipid profile. Therefore, caution must be made in applying these results to a more heterogeneous population. However, within confines of these limitations, the results suggest that both maintenance of a favorable fat distribution and aerobic fitness may be important strategies for healthy aging, at least in premenopausal AA and EA women.
In previous studies, the negative relationship of leg fat with cardiometabolic risk only occurred after adjusting for trunk fat, IAAT, or total fat (9
). In fact, leg fat has usually been positively related to increased risk for CVD and type 2 diabetes when no adjustments were made (9
). This was not the case in this study. Leg fat was negatively related to fasting insulin and all blood lipids, except HDL-C for which it was positively related. In addition, it was positively related to Si
(). It continued to be significantly and inversely related when expressed as a ratio (leg fat-IAAT) or after adjustments in a linear regression (). Our analysis in which subjects were divided into low and high IAAT, and low and high leg fat groups further supports the potential importance of leg fat in improving blood lipid profile and Si
(). The group that had relatively low IAAT and relatively high leg fat consistently had the best blood lipid profile, fasting insulin, and Si
. Of particular note is that the high IAAT/high leg fat group actually had a better fasting blood lipids, Si
, and blood lipid profile (with the exception of HDL-C and cholesterol-HDL ratio) than the high IAAT/low leg fat group (). Regardless of IAAT increases, increased leg fat seems to be related to improved blood lipid profile and Si
in these women.
IAAT may be associated with increased risk of CVD and type 2 diabetes through its detrimental effect on metabolism in the liver. Hepatic insulin extraction is decreased when exposed to increases in IAAT-derived free fatty acids, which in turn leads to increased fasting insulin. Both risk for CVD and type 2 diabetes is thus increased. On the other hand, leg fat has been proposed to have a protective effect because it has a low rate of lipolysis (40
) when compared to IAAT, and may act as a sink for storing fat, thus improving lipid profile and Si
). A relatively new alternative hypothesis for explaining the positive relationship between IAAT, and blood lipids and Si
may involve a larger production of cytokines in IAAT (41
). IAAT is associated with the pro-inflammatory cytokine tumor necrosis factor-α and its receptors tumor necrosis factor-RI and tumor necrosis factor-RII, whereas subcutaneous body fat is not associated with this cytokine in premenopausal overweight women (42
). In addition, tumor necrosis factor-α has been implicated with a reduction in insulin signaling (43
), suggesting that inflammation is associated adversely with Si
The data from the present study do not necessarily show cause and effect between leg fat, and blood lipids and Si
, but do lend support for the intriguing possibility that leg fat may convey a protective effect on individuals with genetic propensity to store fat in the gluteofemoral region. Another equally plausible explanation for an apparent protective effect of leg fat involves the endocrine environment. It is possible that women who tend to deposit fat in the legs when they gain weight may have a particular hormone profile that is protective. For example, a more estrogenic environment may direct fat storage toward the legs, whereas a more androgenic environment may direct fat storage toward IAAT (45
). Estrogens also have a beneficial effect on lipid profile and Si
through action on lipid metabolism and glucose uptake (46
The inverse association between aerobic fitness and blood lipids is highly consistent across studies (49
). Low aerobic fitness is considered a predictor of CVD as well as low Si
) and all-cause mortality in both men and women (52
). We found that aerobic fitness was an independent predictor of HDL-C, cholesterol-HDL ratio, TGs, and Si
(). It is important to point out that this is the first time that these relationships with aerobic fitness have been shown to be independent of fat distribution and African admixture in a mixed population of AA and EA women. Aerobic fitness has a genetic component as well as a training component, but it is impossible to separate their respective contributions to blood lipids and Si
in this study.
Consistent with the results of Arsenault et al.
), it is important to point out that women in the highest tertile for aerobic fitness had lower IAAT than women in the lowest tertile for aerobic fitness even after adjusting for percent body fat, suggesting exercise training may have a positive effect on maintaining a favorable fat distribution (). If this is the case, aerobic fitness would possibly have both an independent effect on blood lipids and Si
(as shown by the relationships discussed in the previous paragraph), and an indirect one through improvement of fat distribution.
Inclusion of AFADM as a covariate strengthened this study because we accounted for the ancestral genetic variation that underlies racial classification, and we did not limit our design to a dichotomous (AA or EA) race variable. The worsened metabolic profile found with increased IAAT and improved metabolic profile found with increased leg fat were unaffected by adjustments for AFADM. After adjustments for fat distribution, aerobic fitness, and age, AFADM was related to an improved lipid profile (positive relationship with HDL and negative relationship with cholesterol-HDL ratio and TGs) but lower Si and higher fasting insulin. Thus, aside from any genetic contribution to fat distribution and aerobic fitness, genetic differences still account for variability in cardiometabolic profile.
In conclusion, our findings suggest that IAAT is a consistent independent predictor of increased worsened blood lipid profile, fasting insulin, and Si, whereas leg fat and aerobic fitness are consistent independent predictors of improved blood lipid profile, fasting insulin, and Si in a mixed group of EA and AA premenopausal women. Age was not related to any blood lipid after adjustments were made for fat distribution and aerobic fitness. However, age was related to decreased fasting insulin and increased Si after adjusting for aerobic fitness and fat distribution in these premenopausal EA and AA women.