The major new finding of the present study is that modest diet-induced weight gain results in increases in large artery stiffness in healthy young adult males. Those individuals with relatively larger increases in abdominal visceral fat demonstrated correspondingly larger increases in arterial stiffness and greater reductions in arterial compliance. Importantly, the adverse effect of abdominal visceral fat accumulation on arterial stiffness and compliance occurred independent of the amount of total body fat gained.
The results of previous prospective studies regarding the determinants of arterial stiffening are inconsistent with respect to the role of weight gain. Wildman et al. found weight gain over a two-year period to be associated with an increase in pulse-wave velocity among healthy young adults whereas Benetos et al. 19, 20
failed to support such an association. The reasons for these disparate findings remain unclear, but may be explained, in part, by the inclusion of older subjects (>50 years) by Benetos et al. 19
. Nonetheless, our current findings confirm and extend the findings of Wildman et al. 20
by demonstrating that experimental weight and fat gain, particularly in the abdominal visceral region, is associated with an increase in arterial stiffness in healthy young males.
Numerous cross-sectional studies report associations between surrogate (i.e., waist circumference) and direct measures of visceral adiposity and large artery stiffness across a variety of subject populations 6-12
. Most notably, abdominal visceral fat (measured via computed tomography) appears to be the strongest predictor of aortic stiffness 10, 11
. Taken together with these previous cross-sectional studies, our findings implicate abdominal fat partitioning as an important mediator of the arterial stiffening that occurs with weight gain.
The mechanisms linking abdominal visceral fat and arterial stiffening are unclear, although numerous possibilities have been advanced 27
. Seals and Gates 28
hypothesized that the pro-inflammatory state and oxidative stress accompanying weight gain (and aging) alters vascular structure and function by disrupting the balance of key extracellular matrix proteins (i.e., elastin and collagen), vasoconstrictive and vasodilatory molecules (e.g., nitric oxide, prostacyclins, endothelin-1, and angiotensin-II), and promoting vascular smooth muscle cell hypertrophy. Together these pathophysiological mechanisms lead to arterial stiffening. Given the short duration of the present study, it seems unlikely that structural modifications to the vasculature, as observed in age-associated arterial stiffening, can account for the increase in stiffness observed following weight gain. A more plausible explanation is that a multitude of interrelated factors sensitive to acute changes in body weight including reductions in insulin sensitivity, dyslipidemia, activation of the sympathetic nervous and renin-angiotensin systems and perhaps other factors conspire to impair endothelial function (i.e., increase vascular smooth muscle tone) and, in turn, results in arterial stiffening 27
. However, we found no association between the changes in carotid stiffness or compliance and changes in estimates of insulin sensitivity (i.e., fasting insulin and HOMA score), plasma renin activity, or muscle sympathetic nerve activity (22
; data not shown). We should emphasize that our study was not designed to address potential mechanisms. As such, future studies will be necessary to address this important issue.
There are some limitations of the present study that should be discussed. First, we did not include a control group and our sample size was relatively small. Thus, inclusion of a control group and/or a larger sample size may have yielded different results. However, that 11 out of the 14 subjects demonstrated an increase in carotid artery stiffness following weight gain and, as hypothesized, the subjects with the largest increase in abdominal visceral fat (manipulated variable) also demonstrated the largest increase in arterial stiffness (the outcome variable), suggests that our results are unlikely to have been the results of random deviations over time.
Second, the subjects in the present study were limited to young, nonobese males. Females tend to accumulate fat in the gluteal-femoral regional and older adults are more susceptible to visceral fat accumulation. As such, the vascular responses to weight gain may be attenuated or amplified, respectively. For these reasons, caution should be taken in extrapolating our findings to females or beyond the age-range studied.
Third, the experimental weight gain produced in the present study may not be representative of the more gradual changes that occur over time in the general population. As such, our findings should be considered with this in mind.
Finally, we should emphasize that our findings do not preclude the possibility that the expansion of other fat depots, such as perivascular adipose tissue, may play an important role in mediating the effects of weight gain on arterial stiffness 29
In conclusion, the results of the present study indicate that modest diet-induced weight gain results in large artery stiffening in young, nonobese males. Those individuals who demonstrated the largest increases in abdominal visceral fat also demonstrated the largest increases in arterial stiffness. Importantly, the increase in arterial stiffness associated with abdominal visceral fat accumulation occurred independent of the amount of total body fat gained.