The purpose of this study in healthy overweight premenopausal AA and C women was to examine potential ethnic differences in markers of inflammation and regional fat distribution with weight loss, and to identify the associations between changes in these markers and changes in regional fat distribution. We found that markers of inflammation decreased following weight loss; however responses differed between AA and C women. Specifically, all markers of inflammation decreased following weight loss in C women, whereas only IL-6 and CRP decreased following weight loss in AA women. The ethnic differences observed for TNF-α between C and AA women were due in part to the greater loss of IAAT in C women. These observations suggest that there are ethnic differences among premenopausal AA and C women in the association between changes in regional fat distribution and markers of inflammation with weight loss.
We initially speculated that greater baseline IAAT and greater baseline TNF system markers among C women would result in greater changes in these measures with weight loss. We observed that C women had a greater loss of both IAAT and TNF-α with weight loss compared to AA. In fact, in C women circulating concentrations of the TNF system decreased with weight loss to levels comparable to those of their AA counterparts (). Furthermore, statistically adjusting for change in IAAT attenuated the ethnic difference in change in TNF-α (P=0.135 for ethnicity; P=0.056 for ethnicity*time interaction; ). Both of these findings suggested that the change in TNF-α in C women was in part due to the loss of IAAT in this population.
We also observed an ethnic difference in the change in sTNF-RI and sTNF-RII with weight loss. C women showed decreases in both sTNF-RI and sTNF-RII, whereas AA women showed no changes in these measures. Although it is tempting to speculate that this ethnic difference was likewise attributable to greater IAAT in the C, we did not observe a significant association between the change in IAAT and the changes in the receptors. Further, inclusion of measures of body fat in the multiple regression models did not eliminate the significant effect of ethnicity.
To further probe the mechanism for the differential change in receptors between AA and C with weight loss, we examined the possibility that lean body mass played a role. Lower levels of sTNF-RI and sTNF-RII have been reported in lean compared to obese individuals (26
). In our cohort, AA tended to show a preservation of lean mass with weight loss, whereas C tended to show a decrease (P
=0.089 for ethnicity*time interaction; ). However, when change in lean mass was included in the models for sTNF-RI and sTNF-RII, ethnicity was still a significant determinant. Thus, the mechanism through which weight loss alters the TNF receptors in C women cannot be determined from our results.
Whether a decrease in TNF receptors indicates an improvement in metabolic health is not entirely clear. TNF-α is thought to exert its biological effects on cell function by binding to cell surface receptors sTNF-RI and II (27
). The extracellular portions of these receptors are present in serum as sTNF-RI and sTNF-RII, and are thought to reflect TNF-α activity. sTNF-RI is thought to mediate the metabolic actions of TNF-α, such as its effects on insulin signaling (28
), while the role of sTNF-RII is less clear. These receptors are usually elevated in obese individuals compared to lean controls (26
). However, weight loss studies have yielded equivocal results; Zahorska-Markiewicz et al. (2000) found a significant increase in both sTNF receptors following weight loss (31
), while Bastard et al. (2000) found a significant decrease in sTNF-RI and no change in sTNF-RII (32
). In our study, the receptors either decreased (C women) or remained unchanged (AA women). Differences among studies may be due to the energy balance status of the subjects.
In the present study we found no significant differences in IL-6 or CRP between ethnic groups at baseline or following weight loss. The parallel responses of IL-6 and CRP were not unexpected since secretion of CRP by the liver is primarily regulated by circulating IL-6 (33
). The current literature examining ethnic differences in circulating IL-6 and CRP is discrepant. Cross sectional studies have reported both significant (15
), and non-significant (12
) differences in IL-6 and CPR between AA and C women. Visceral fat is often mentioned as the primary site of IL-6 secretion (34
). However, in our sample, greater IAAT in C did not correspond to greater IL-6, suggesting that IL-6 may be released from other fat depots. This hypothesis is reinforced by the observation that adjustment for total fat but not IAAT eliminated the “time” effect in the mixed model for IL-6 (data not shown). Further, we found no significant associations of IAAT with IL-6 and CRP. While no significant associations between IAAT and IL-6 were observed, the possibility that the feedback loop involving IL-6 may not simply be related to the amount of adipose tissue but rather other stimuli can not be disregarded.
The current study revealed several areas for further evaluation. Ethnic differences have been reported for many variables, including fat distribution, insulin sensitivity, disease risk, and the TNF system. The present study also showed ethnic differences in the relationships between markers of inflammation and fat distribution. An unexamined possibility is that markers of inflammation have a different effect on adipose tissue in C vs. AA women. For example, TNF-α has autocrine functions in tissues where it is expressed, as well as more systemic paracrine functions in tissues that express the receptors for it. Because C had greater circulating TNF-α and its receptors than AA, it is possible the TNF system may be of greater physiological relevance among obese/overweight C women relative to AA.
Strengths of this study included robust measures of body composition and body fat distribution. Additional strengths included closely matching the number of AA (n = 65) and C (n = 61) women and taking post-weight loss measures after 4-weeks of weight maintenance. To our knowledge this is the first sufficiently powered longitudinal study to examine changes in regional fat distribution and markers of inflammation following weight loss among AA and C women. A limitation in this study was not examining all relevant lipid depots, such as intermuscular adipose tissue and intramyocellualar lipid. Furthermore, our results are limited to a population of healthy, overweight, premenopausal women. Similar studies on men, obese individuals, children, and postmenopausal women should be performed.
In conclusion, we demonstrated that weight loss reduces markers of inflammation in overweight premenopausal AA and C women. However, the changes in these markers following weight loss differed between ethnic groups. We found that all markers of inflammation decreased following weight loss among C, whereas only IL-6 and CRP decreased following weight loss in AA. The most distinct phenotypic difference observed in this study was a greater impact of weight loss on TNF-α in C women compared to AA women, which was directly associated with IAAT in C women. Therefore, despite the higher prevalence of some metabolic diseases in AA vs C (e.g., hypertension, type 2 diabetes), our data suggest that, regarding inflammation, weight loss may have stronger health benefit among C when compared to AA women, in part due to the greater loss of visceral fat in C women. Thus, health care providers should continue to emphasize the importance of weight loss, even among demographic groups such as young C women often assumed to be at relatively low risk for chronic metabolic disease. Further study is needed to examine the progression of low grade inflammation on the pathogenesis of chronic diseases, and how these processes differ with ethnicity