Gene findings suggest biologic asthma–obesity link
medwireNews: Researchers have discovered a biologic mechanism behind the association between asthma and obesity.
The team identified several genes associated with chronic inflammation in asthma that are more highly expressed in obese individuals than those at a healthy weight. And, in morbidly obese patients with Type 2 diabetes, weight loss following gastric bypass surgery was accompanied by parallel decreases in expression of these genes.
“There has been, until now, no biological, mechanistic explanation other than the fact that obesity may raise the diaphragm and thus reduce lung volumes,” said lead author, Paresh Dandona (State University of New York at Buffalo, New York, USA) in a press statement.
He added: “Our findings point the way to the management of asthma in the obese through simple weight reduction.”
Among 23 obese patients (mean body mass index [BMI] 35.5 kg/m2; 11 with diabetes) and 15 morbidly obese patients with Type 2 diabetes (mean BMI 52.1 kg/m2), expression of interleukin (IL)-4, matrix metalloproteinase (MMP)-9, and chemokine receptor (CCR)-2 messenger RNA in mononuclear cells was significantly higher than among 22 healthy-weight participants.
And levels of LIGHT, a recently described ligand that is involved in bronchial remodelling, were also significantly greater in all obese participants, as were plasma levels of nitric oxide metabolites (NOM; NO2/NO3) and MMP-9.
“Since these are key mediators involved in the pathogenesis of allergy and asthma, the increase in their expression and plasma concentrations may contribute to the increased vulnerability and risk of asthma in the obese,” comment the authors.
Morbidly obese patients with Type 2 diabetes had the highest levels of gene expression and plasma concentrations. Following Roux-en-Y gastric bypass in these 15 patients, the researchers observed significant reductions in bodyweight, BMI, and improvements in diabetes-related parameters such as glucose, insulin and glycated hemoglobin, as well as reductions in major oxidative and inflammatory markers.
This was accompanied by significant decreases in the mononuclear cell expression of IL-4, LIGHT, MMP-9, and CCR-2 by 49%, 29%, 59%, and 27%, respectively. Levels of other asthma-related mediators, including ADAM33 (disintegrin and metalloproteinase domain-containing protein 33), LTBR (the receptor that binds LIGHT), and MCP-1 (monocyte chemoattractant protein 1) also significantly decreased, and levels of plasma NOM and MMP-9 fell by 22% and 26%, respectively.
The authors say that as their study did not include patients with asthma, further research is needed to apply the results to obese patients with asthma.
“If these changes in gene expression are reflected in the clinical changes in the patient, they may provide a useful indication of the clinical activity of asthma,” the authors, who say they have begun work on such a study, write in Obesity.
“Gastric bypass surgery may provide a potential therapeutic approach to asthma in the morbidly obese,” they add.
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By Kirsty Oswald, medwireNews Reporter