Effect of Weight Loss on Proinflammatory State of Mononuclear Cells in Obese Women

Abstract

TO THE EDITOR: The recent article in this Journal by Sheu et al. (1) titled “Effect of Weight Loss on Proinflammatory State of Mononuclear Cells in Obese Women” addresses the important question of whether weight loss alters the proinflammatory state associated with obesity. The authors used serum levels of several proinflammatory markers such as C-reactive protein and tumor necrosis factor-α, as well as proinflammatory gene transcript levels and nuclear factor-κB (NFκB) DNA binding in peripheral blood mononuclear cells (MNCs), as biomarkers of the systemic inflammatory response. It was reported that a small degree of weight loss (5%), induced by a 12-week calorie restriction and exercise program, was associated with marked reductions in circulating levels of most proinflammatory markers (but not interleukin-6) and reduced NFκB “activity” in MNCs (1). We were rather surprised by the dramatic decrease in serum C-reactive protein levels induced by this small degree of weight loss (mean BMI following weight loss was still 30.6 kg/m), particularly when the mean serum level of interleukin-6 (the direct upstream regulator of C-reactive protein synthesis) actually increased over the same period. One speculates that a behavioral change linked to the weight loss program, such as dietary intake (2) or exercise (3), or other confounding clinical factors, rather than weight loss per se, might have contributed to the observed changes in inflammatory biomarkers. To this end, it is important to exclude nonsteroidal anti-inflammatory drug use or intercurrent infection as contributing factors in this study. It would also be interesting to analyze the same inflammatory biomarkers several weeks after the end of the weight loss program to further interpret these short-term biomarker changes. The relevance of the observed changes in transcript levels for the NFκB and IκB isoforms to downstream NFκB-dependent transcriptional activity in MNCs is uncertain, and it is unfortunate that the protein expression data were not included in the article, particularly as NFκB DNA binding data were presented. We urge caution in interpretation of quantitative changes in p65/p50 DNA binding on the basis of a mobility shift assay alone, particularly when there is variable nuclear extract loading evident and the appropriate controls are not presented. It should be noted that colorimetric NFκB DNA-binding assays are now available commercially for more accurate quantification. Finally, we note that data from lean and obese subjects (before and after weight loss) were combined for multiple correlation analyses between serum/MNC biomarkers and BMI, as well as insulin resistance. This approach is questionable as the biological relationship between these factors may alter in these different clinical contexts. The preliminary findings by Sheu et al. should now be confirmed in a well-defined cohort of obese patients undergoing a greater degree of weight loss to determine the use of MNCs for future human biomarker studies in obesity research.