The purpose of this study in healthy overweight premenopausal women was to identify the independent effects of energy restriction alone and energy restriction in combination with exercise on changes in MOI, and whether these changes were associated with changes in body composition or regional fat distribution. The main findings were that: (i) weight loss was associated with significant decreases in MOI; (ii) the addition of aerobic or resistance exercise to the energy restriction paradigm did not alter the outcome; and (iii) the decrease in MOI were strongly associated with changes in IAAT and total fat mass. These observations suggest that regardless of weight loss method (with or without exercise), loss of total and/or intra-abdominal fat mass was most strongly associated with improvements in inflammatory status.
Chronic inflammation is an important cause of cardiovascular disease, and is strongly associated with obesity and metabolic dysfunction (22
). Current literature suggests that adipose tissue macrophage density increases with obesity, reducing production of anti-inflammatory adipokines, and increasing secretion of proinflammatory cytokines (24
). Several studies have documented that weight loss in conjunction with energy restriction (7
), surgery (27
), or exercise (16
) can improve both body composition and MOI. However, the independent effects of energy restriction and exercise on MOI have not been well documented. Prior investigations have not provided a clear picture; studies have shown that exercise training induces improvements in inflammation independent of BMI (11
) and others that suggest weight loss-associated reductions in inflammation are independent of exercise (10
). The lack of a control group (diet only) in the majority of these studies has been a major limitation when trying to identify the independent effects of exercise on inflammation (11
In this study, we utilized a diet-only control group in conjunction with diet/aerobic- and diet/resistance exercise training groups in order to determine whether the addition of exercise to a weight-reducing diet would result in greater improvements in MOI and body composition compared to a weight-reduced diet alone. Our mixed-model analysis revealed no effect of intervention group (diet only, diet/aerobic, or diet/resistance) on MOI (), suggesting that the intervention type was not independently related to decreases in inflammation with weight loss. Instead, time was a significant predictor in all models, suggesting that weight loss was primarily responsible for the decrease in MOI ( and ). This is in agreement with the two other sufficiently powered-randomized clinical trials that examined the independent effects of exercise and weight loss on MOI in a cohort of men and women (10
). Both studies found no independent effect of exercise on MOI. Furthermore, when taking into account differences in study designs, it appears that when exercise interventions are used independently (without diet) there are significant improvements in inflammation (30
). However, when exercise is incorporated with dietary weight loss (10
) or exercise training is performed without any significant weight loss (31
) the exercise effect is reduced or lost completely. us, it appears that the effect of exercise on MOI is primarily due to reductions of fat mass rather than a specific effect of exercise alone.
This study was also designed to more closely examine the relationship between changes in body composition with MOI. It has previously been shown that changes in IL-6 and CRP were independent of changes in BMI (10
). However, the use of BMI is a limitation because BMI is not a measure of body composition or fat distribution. Body composition measures alone do not differentiate between specific fat depots, therefore prior investigations were unable to assess independent associations between inflammation and fat distribution. The present study utilized dual-energy X-ray absorptiometry and computed tomography imaging to examine the influence of fat distribution on MOI. It has been well documented that IAAT is associated with elevated MOI (13
). Our results are in agreement with this, as we found that decreased MOI (IL-6, CRP, TNF-α, sTNF-R1, and sTNF-R2) following weight loss could be explained by total fat mass and/or IAAT ( and ). Therefore, within our population of premenopausal women, MOI were linked with adiposity.
It has been well documented that a negative energy balance generated from either exercise or diet elicits a very potent anti-inflammatory effect (7
). The majority of these studies obtained postweight loss measurements while the subjects were still in negative energy balance, making it difficult to identify the independent effects of the diet and/or exercise-induced changes in body composition or anti-inflammatory effects of contracting skeletal muscle from the effects of negative cellular energy balance. It seems plausible that once the participants in these studies reestablished energy balance, the inflammatory profile may return to preintervention levels. In order to eliminate the potential confounding effects of negative energy balance on MOI, we incorporated a 4-week postweight loss intervention diet in order to obtain an energy-balanced state before blood sampling. Therefore, we are able to conclude that changes in MOI in this study were due to reductions in total fat mass and/or IAAT not negative energy balance. It appears that decreasing adiposity from diet and/or exercise is an effective means for reducing circulating MOI.
Strengths of this study included robust measures of body composition and body fat distribution. Postweight loss measures were taken after participants were placed on a 4-week diet, which was designed to ensure an energy-balanced state (eliminating the potential independent effects of negative energy balance on metabolic outcomes). Further strengths of the study were the inclusion of a dietary control group in conjunction with diet/exercise groups enabled us to assess the independent and combined effects of diet and exercise. A limitation in this study was the absence of an exercise group that did not lose weight. Based on previous studies (11
) it is very possible that exercise by itself may have had a positive affect on cytokines. Further studies are needed to separate the independent effects of weight loss vs. exercise. Additionally, our results are limited to a population of healthy, overweight, premenopausal women. Similar studies on men, obese individuals, children, and post-menopausal women would be of interest.
In conclusion, the overall implication from the present study was that loss of total and visceral fat was the biggest contributor to decreases in circulating MOI with weight loss, and that resistance and aerobic exercise training did not have a further independent effect on inflammation. Further research is needed to examine the potential differences between anti-inflammatory cytokines that may be released from skeletal muscle during exercise and proinflammatory cytokines associated with adiposity, immune dysfunction, and chronic diseases.