Increase in the mediators of asthma in obesity and obesity with type 2 diabetes: Reduction with weight loss

Abstract

Objective: To determine whether the expression of key asthma related genes, IL-4, LIGHT, LTBR, MMP-9, CCR-2, and ADAM-33 in mononuclear cells and the plasma concentration of nitric oxide metabolites (NOM) and MMP-9 are increased in the obese, obese type 2 diabetics (T2DM) and in morbidly obese patients prior to and after gastric bypass surgery (RYGB). Design and Methods: The expression of these genes in MNC and plasma concentrations of these indices was measured in healthy lean and in obese with and without T2DM and following RYGB in obese T2DM.Results: The expression of IL-4, MMP-9, LIGHT and CCR-2 and plasma NOM concentrations was significantly higher in the obese subjects and in obese T2DM patients than in normal subjects. The expression of IL-4, LIGHT, MMP-9, and CCR-2 expression was related to BMI and HOMA-IR. The expression of IL-4, LIGHT, LTBR, ADAM-33, MMP-9, and CCR-2 fell after RYGB surgery as did plasma concentrations of MMP-9 and NOM. Conclusions: Obesity with and without T2DM is associated with an increase in the expression of IL-4, LIGHT, MMP-9 and CCR-2; plasma NOM and MMP-9 concentrations are also increased. Following RYGB surgery and weight loss, the expression of these factors in MNC and plasma concentrations falls significantly.

Shining LIGHT on the metabolic role of the cytokine TNFSF14 and the implications on hepatic IL‐6 production

“…There is mounting evidence indicating the beneficial effects of the cytokine TNFSF14 in disease . However, the role of TNFSF14 in the development of obesity and type 2 diabetes remains poorly understood . Our novel findings provide clear evidence that TNFSF14 is elevated in mice as an adaptive response to attenuate characteristics of the metabolic syndrome.…”

“…Currently controversy surrounds the role of TNFSF14 in the development of the metabolic syndrome. Serum TNFSF14 levels are reportedly increased in morbidly obese humans and the expression of TNFSF14 is reduced in patients who do not have T2D compared with type 2 diabetic patients . However, it remains to be elucidated whether TNFSF14 is functionally altered in the progression of the metabolic syndrome in a pro‐ or anti‐obesogenic manner.…”

Indications for Surgery for Obesity and Weight-Related Diseases: Position Statements from the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO)

“…A recent study by Dandona et al demonstrated that following GBP and weight loss, there is a reduction in the expression of key genes involved in asthma pathogenesis including IL-4, MMP-9, LIGHT, LTBR, and ADAM-33 [134]. Because of these changes in gene expression, GBP may provide a potential therapeutic approach to asthma in the morbidly obese.…”

Multifaceted Breast Cancer: The Molecular Connection With Obesity

“…Leitner et al () observed a deep increase of MMP‐9 levels in adipose tissue from obese donors, which improve Osteopontin (OPN) inflammatory and pro‐diabetic effects on adipocytes. Dandona et al () also found high levels of MMP‐9 in plasma from obese patients, with or without diabetes, directly associated with plasma nitric oxide metabolites levels positively related with responsivity to surgical therapy. Rouault et al () observed that blood neutrophils from obese subjects release high levels of MMP‐9 and other pro‐inflammatory mediators (IL‐8, CCL2, MPO, etc.)…”