Plasma Leptin Levels, Obstructive Sleep Apnea Syndrome, and Diabetes Are Associated with Obesity-Related Alterations of Peripheral Blood Monocyte Subsets

Abstract

Obesity is a dramatically increasing disease, accompanied with comorbidities such as cardiovascular disease and obstructive sleep apnea syndrome (OSAS). Both obesity and OSAS per se are associated with systemic inflammation. However, the multifactorial impact of obesity, OSAS, and its concomitant diseases on the immunological characteristics of circulating monocytes has not yet been fully resolved. Monocyte subsets of 82 patients with obesity were analyzed in whole blood measurements in terms of the CD14/CD16 cell surface expression patterns and different monocytic adhesion molecules using flow cytometry. Plasma levels of adipokines adiponectin and leptin of all patients were evaluated and correlated with accompanying cellular and clinical values. Whole blood measurements revealed a significant overall redistribution of CD14/CD16 monocyte subsets in patients with obesity. Monocytic adhesion molecules CD11a, CD11b, and CX3CR1 were significantly elevated. The observed alterations significantly correlated with plasma leptin levels and diabetes status as crucial amplifying factors. The additive impact of obesity, diabetes, and OSAS on the immunological balance of peripheral blood monocytes requires a coordinated regimen in terms of therapeutic treatment, respiratory support, and weight loss to improve the systemic immunity in these patients.

Distinguishing the impact of distinct obstructive sleep apnea syndrome (OSAS) and obesity related factors on human monocyte subsets

“…Moreover, our data revealed significantly elevated plasma leptin levels in the obesity cohort and a significant positive correlation with the BMI values. These data corroborate earlier data with regard to obese patients with OSAS 16 . It is well known that leptin is secreted by white adipose tissue in direct relation to fat mass and involved in the regulation of cellular inflammatory processes 41 – 43 .…”

“…Expression levels of adhesion molecule CD11c were oppositely affected in the obesity cohort as compared to normal weight patients with OSAS and patients with OSAS and obesity and thus further disentangle recent data on monocytic adhesion molecules in obese patients with OSAS 16 . It has been shown in patients with obesity, that CD11c + innate immune cells in adipose tissue are involved in the formation of an inflammatory state and insulin resistance 20 .…”

“…In order to distinguish these overlapping diseases, whole blood analyses were performed from normal weight OSAS patients, patients with obesity but without OSAS, and patients with OSAS and obesity as compared to healthy donors. Analyses revealed highly significant redistributions of circulating classical monocytes and intermediate monocytes in all three patient cohorts, which underlines that both conditions favor a low-grade systemic inflammation and immune alterations 2 , 3 , 16 . These findings corroborate recent data where monocyte subset distributions of OSAS patients could be normalized by therapeutic hypoglossal nerve stimulation (HNS) and the corresponding positive effects on the peripheral blood oxygenation 18 .…”

“…Our recent data revealed significantly decreased abundances of circulating classical monocytes accompanied by increased percentages of intermediate and non-classical monocytes in people with severe obesity (BMI ˃ 35 kg/m 2 ). Plasma leptin levels, obstructive sleep apnea syndrome and diabetes status of these patients were identified as crucial amplifying factors, which underlines the impact of these comorbidities on the systemic immunity 16 .…”

“…Distribution and expression of adhesion molecules from normal weight OSAS patients and patients with obesity but without OSAS were compared with patients with OSAS and obesity, which have already been analyzed in an earlier publication 16 . The clinicopathological characteristics of patients with OSAS and obesity are listed in Table 3 .…”