Peripheral monocytes of obese women display increased chemokine receptor expression and migration capacity. Krinninger P1, Ensenauer R, Ehlers K, Rauh K, Stoll J, Krauss-Etschmann S, Hauner H, Laumen H. J Clin Endocrinol Metab. 2014 Jul;99(7):2500-9
The activation of peripheral immune cells and the infiltration of immune cells into adipose tissue in obesity are implicated in the development of type 2 diabetes mellitus. In this study peripheral immune cells from obese and normal-weight women were compared with regard to composition of immune cell subpopulations, surface expression of the chemokine receptors (CCRs) CCR2, CCR3, CCR5, and CXCR3 (chemokine (C-X-C motif) receptor 3) and cell-intrinsic migration capacity. Obese females and normal-weight females were included for fluorescence-activated cell sorting analysis and migration assays. Peripheral blood mononuclear cells were prepared from fasting blood samples. An increase in the percentages of CD14(+)CD16(+) monocytes was observed in obese subjects compared with controls. The CCR profile of monocytes differed significantly in the obese state; in particular, CCR2 levels were increased. In addition, a higher chemotactic activity of monocytes from obese subjects was observed in a migration assay, which was associated with both insulin resistance and CCR2 expression. Conclusion: The results suggest that the enhanced intrinsic migratory capacity of peripheral monocytes in obese women may be due to the increased CCR expression, further supporting a link between peripheral immune cell dysfunction and obesity.
COMMENT-The obese subjects had an increased proportion of CD14+CD16+ circulating monocytes, that can secrete pro-inflammatory cytokines on activation. This, along with other evidence, supports a role for general immune activation as part of the low-grade inflammatory process seen in adipose tissue in obesity.
Bacterial DNA translocation holds increased insulin resistance and systemic inflammatory levels in morbid obese patients.Ortiz S1, Zapater P, Estrada JL, Enriquez P, Rey M, Abad A, Such J, Lluis F, Francés R. J Clin Endocrinol Metab. 2014 Jul;99(7):2575-83
Morbidly obese patients show several common comorbidities associated with immunological alterations such as a sustained low-level proinflammatory profile. Bacterial product translocation is frequent in inflammation-related diseases and may aggravate patients' clinical outcome. Consecutively admitted morbidly obese patients who presented indications for bariatric surgery were studied. Before surgery, patients were subjected to a modified fasting diet. Patients (58) underwent surgery by sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass. Blood samples were collected at baseline, at the end of a 3-month modified fasting period, and 3, 6, and 12 months after surgery. Serum cytokine and endotoxin levels were evaluated by flow cytometry and ELISA, respectively. Bacterial DNA was identified in blood by broad-range PCR of prokaryote 16SrRNA gene and partial sequencing analysis.
All patients showed a significantly reduced weight and body mass index at each time-point. Postoperative mortality was null. Bacterial DNA translocation rate was 32.8% (19 of 58) at baseline; 13.8% (8 of 58) after the modified fasting period; and 13.8% (8 of 58), 1.8% (1 of 58), and 5.2% (3 of 58) at 3, 6, and 12 months after surgery. Proinflammatory cytokines, serum endotoxin levels, and insulin resistance remained increased in patients with bacterial DNA despite weight loss and were individually affected by the appearance/clearance of bacterial DNA in blood. Multivariate analyses revealed bacterial DNA as an independent significant factor, explaining the systemic cytokine response and the insulin resistance levels in the studied population. Bacterial DNA translocation “holds” increased insulin resistance and systemic inflammatory levels in morbidly obese patients despite significant weight loss.
COMMENT- This study indicates that gut bacterial DNA is at least transiently present in blood of 30% of obese indiviuals, and is related to the low-grade inflammatory state of morbid obesity. While inflammatory markers generally declined after surgery, their persistence was associatecd with maintenance of the inflammatory state.