Influence of weight reduction on blood levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and oxylipins in obese subjects.

INTRODUCTION

Obesity is associated with inflammation and weight reduction has been shown to influence the inflammatory process. Besides classic inflammatory markers, oxidized polyunsaturated fatty acid (PUFA) metabolites (oxylipins) are potent mediators of inflammation. Little is known about endogenous levels of oxylipins, e.g. hydroxy, epoxy and dihydroxy FA in obese subjects with persistent low-grade inflammation. We aimed to evaluate levels of inflammatory markers and blood oxylipins in obese subjects before and after weight reduction.

SUBJECTS AND METHODS

In the present study, 42 obese (BMI 32.7 ± 0.22 kg/m(2)) men and women were classified in groups according to high-sensitivity C-reactive protein (hsCRP) levels (no inflammation<1mg/L; low-grade inflammation ≥ 3 mg/L). Subjects underwent an intervention for eight weeks, which consisted of two phases: (1) week 1 and 2: total replacement of three meals by a formula diet and (2) six week partial formula diet (replacement of 1-2 meals). Blood samples were taken prior and post intervention for analysis of plasma protein levels of hsCRP, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Plasma Levels of free (unesterified) hydroxy, epoxy, and dihydroxy FAs as well as several prostanoids were analyzed in plasma by means of LC-MS-based targeted metabolomics.

RESULTS

At baseline subjects with low-grade inflammation (hsCRP 8.95 ± 1.39 mg/L) showed significant higher levels of IL-6 (22.7 ± 1.15 ng/L) and TNF-α (17.4 ± 0.75 ng/L) compared to subjects with no inflammation (hsCRP: 0.69 ± 0.05 mg/L; IL-6: 15.9 ± 1.18 ng/L; TNF-α: 14.6 ± 0.80 ng/L). In both group's body weight was significantly reduced (p<0.001) after intervention (no inflammation group: -7.19 ± 0.86 kg, -7.3 ± 0.89%, p<0.001; low-grade inflammation group: -6.78 ± 0.87 kg, -6.7 ± 0.81%, p<0.001). Moreover, we observed significant decreases in levels of hsCRP (4.66 ± 0.64 mg/L; p=0.006), IL-6 (6.81 ± 1.15 ng/L; p<0.001) and TNF-α (6.09 ± 0.47 ng/L; p<0.001) in subjects with low-grade inflammation. Of 60 quantified oxylipins, 11 linoleic acid (LA)-, 1 dihomo-γ-linolenic acid (DGLA)-, 7 alpha linolenic acid (ALA)-, 15 arachidonic acid (AA)-, 8 eicosapentaenoic acid (EPA)- and 18 docosahexaenoic acid (DHA)-metabolites could be detected in plasma. For most oxylipins no differences were found between the low and high hsCRP groups before and after weight reduction. Interestingly, in subjects with low- grade inflammation several AA-derived oxylipins (5-, 8-, 12-hydroxyeicosatetraenoic acids (HETE)) were significantly higher compared to subjects with no inflammation before weight reduction and significantly reduced after weight reduction.

CONCLUSION

Even moderate weight loss in obese subjects correlates to a significant improvement in the inflammatory state, by reducing hsCRP, IL-6, TNF-α and few oxylipins. The biological consequences of these changes remain to be further investigated.