Mounting evidence suggests that obesity, parameters of metabolic syndrome, and asthma are significantly associated. Interestingly, these conditions are also associated with microbiome dysbiosis, ...notably in the airway microbiome for patients with asthma and in the gut microbiome for patients with obesity and/or metabolic syndrome. Considering that improvements in asthma control, lung function, and airway hyperresponsiveness are often reported after bariatric surgery, this review investigated the potential role of bacterial gut and airway microbiome changes after bariatric surgery in ameliorating asthma symptoms. Rapid and persistent gut microbiota alterations were reported following surgery, some of which can be sustained for years. The gut microbiome is thought to modulate airway cellular responses via short‐chain fatty acids and inflammatory mediators, such that increased propionate and butyrate levels following surgery may aid in reducing asthma symptoms. In addition, increased prevalence of Akkermansia muciniphila after Roux‐en‐Y gastric bypass and sleeve gastrectomy may confer protection against airway hyperreactivity and inflammation. Metabolic syndrome parameters also improved following bariatric surgery, and whether weight‐loss‐independent metabolic changes affect airway processes and asthma pathobiology merits further research. Fulfilling knowledge gaps outlined in this review could facilitate the development of new therapeutic options for patients with obesity and asthma.
Asthma patients with comorbid obesity exhibit increased disease severity, in part, due to airway remodeling, which is also observed in mouse models of asthma and obesity. A mediator of remodeling ...that is increased in obesity is leptin. We hypothesized that in a mouse model of allergic airways disease, mice receiving exogenous leptin would display increased airway inflammation and fibrosis.
Five-week-old male and female C57BL/6J mice were challenged with intranasal house dust mite (HDM) allergen or saline 5 days per week for 6 weeks (n = 6-9 per sex, per group). Following each HDM exposure, mice received subcutaneous recombinant human leptin or saline. At 48 h after the final HDM challenge, lung mechanics were evaluated and the mice were sacrificed. Bronchoalveolar lavage was performed and differential cell counts were determined. Lung tissue was stained with Masson's trichrome, periodic acid-Schiff, and hematoxylin and eosin stains. Mouse lung fibroblasts were cultured, and whole lung mRNA was isolated.
Leptin did not affect mouse body weight, but HDM+leptin increased baseline blood glucose. In mixed-sex groups, leptin increased mouse lung fibroblast invasiveness and increased lung Col1a1 mRNA expression. Total lung resistance and tissue damping were increased with HDM+leptin treatment, but not leptin or HDM alone. Female mice exhibited enhanced airway responsiveness to methacholine with HDM+leptin treatment, while leptin alone decreased total respiratory system resistance in male mice.
In HDM-induced allergic airways disease, administration of exogenous leptin to mice enhanced lung resistance and increased markers of fibrosis, with differing effects between males and females.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Asthma is a chronic airway inflammatory disease marked by airway inflammation, remodeling and hyperresponsiveness to allergens. Allergic asthma is normally well controlled through the use of ...beta-2-adrenergic agonists and inhaled corticosteroids; however, a subset of patients with comorbid obesity experience resistance to currently available therapeutics. Patients with asthma and comorbid obesity are also at a greater risk for severe disease, contributing to increased risk of hospitalization. Bariatric surgery improves asthma control and airway hyperresponsiveness in patients with asthma and comorbid obesity, however, the underlying mechanisms for these improvements remain to be elucidated. We hypothesized that vertical sleeve gastrectomy (VSG), a model of metabolic surgery in mice, would improve glucose tolerance and airway inflammation, resistance, and fibrosis induced by chronic allergen challenge and obesity.
Male C57BL/6J mice were fed a high fat diet (HFD) for 13 weeks with intermittent house dust mite (HDM) allergen administration to induce allergic asthma, or saline as control. At week 11, a subset of mice underwent VSG or Sham surgery with one week recovery. A separate group of mice did not undergo surgery. Mice were then challenged with HDM or saline along with concurrent HFD feeding for 1-1.5 weeks before measurement of lung mechanics and harvesting of tissues, both of which occurred 24 hours after the final HDM challenge. Systemic and pulmonary cytokine profiles, lung histology and gene expression were analyzed.
High fat diet contributed to increased body weight, serum leptin levels and development of glucose intolerance for both HDM and saline treatment groups. When compared to saline-treated mice, HDM-challenged mice exhibited greater weight gain. VSG improved glucose tolerance in both saline and HDM-challenged mice. HDM-challenged VSG mice exhibited an increase in airway hyperresponsiveness to methacholine when compared to the non-surgery group.
The data presented here indicate increased airway hyperresponsiveness in allergic mice undergoing bariatric surgery.
Asthma is a common, chronic airway inflammatory disease marked by airway hyperresponsiveness, inflammation, and remodeling. Asthma incidence has increased rapidly in the past few decades and recent ...multicenter analyses have revealed several unique asthma endotypes. Of these, type-2 high asthma with comorbid obesity presents a unique clinical challenge marked by increased resistance to standard therapies and exacerbated disease development. The extrinsic coagulation pathway plays a significant role in both type-2 high asthma and obesity. The type-2 high asthma airway is marked by increased procoagulant potential, which is readily activated following damage to airway tissue. In this review, we summarize the current understanding of the role the extrinsic coagulation pathway plays in the airway of type-2 high asthma with comorbid obesity. We propose that asthma control is worsened in obesity as a result of a systemic and local airway shift towards a procoagulant and anti-fibrinolytic environment. Lastly, we hypothesize bariatric surgery as a treatment for improved asthma management in type-2 high asthma with comorbid obesity, facilitated by normalization of systemic procoagulant and pro-inflammatory mediators. A better understanding of attenuated coagulation parameters in the airway following bariatric surgery will advance our knowledge of biomolecular pathways driving asthma pathobiology in patients with obesity. Keywords: asthma, obesity, coagulation, bariatric surgery, extrinsic pathway, inflammation
We present 126 photometric and 30 spectral observations of SN 1990E spanning from 12 days before B maximum to 600 days past discovery. These observations show that SN 1990E was of type II-P, ...displaying hydrogen in its spectrum, and the characteristic plateau in its light curve. SN 1990E is one of the few SNe II which has been well observed before maximum light, and we present evidence that this SN was discovered very soon after its explosion. In the earliest spectra we identify, for the first time, several N II lines. We present a new technique for measuring extinction to SNe II based on the evolution of absorption lines, and use this method to estimate the extinction to SN 1990E, A(V) = 1.5 +/- 0.3 mag. From our photometric data we have constructed a bolometric light curve for SN 1990E and show that, even at the earliest times, the bolometric luminosity was failing rapidly. We use the late-time bolometric light curve to show that SN 1990E trapped a majority of the gamma rays produced by the radioactive decay of Co-56, and estimate that SN 1990E ejected an amount of Ni-56 virtually identical to that of SN 1987A.
The pharmacological characteristics of the myocardial adrenoceptor of the mouse have been examined during embryogenesis by measuring ornithine decarboxylase (ODC, EC 4.1.1.17) induction. 2 A four ...fold elevation of ODC activity was observed after isoprenaline (10 mg/kg, s.c.), and enzyme activity was increased two to three fold following adrenaline (1 mg/kg, s.c.) or terbutaline given by direct injection to the foetus (10 microgram/500 mg). 3 Pretreatment with the beta-adrenoceptor antagonist, propranolol (10 mg/kg), totally blocked the increase in ODC activity. 4 Elevation of myocardial ODC activity was not inhibited by metoprolol, a relatively specific beta-adrenoceptor antagonist, at a dose of 10 mg/kg. 5 Since the increase in ODC activity was blocked by a beta-adrenoceptor antagonist (propranolol) and enzyme activity was stimulated by terbutaline, a beta 2-agonist, we conclude that beta 2-adrenoceptors are selectively coupled to the regulation of murine cardiac ODC activity following catecholamine stimulation.
We have developed a reproducible model of cardiac hypertrophy in conscious, unrestrained dogs after recovery from surgical trauma. The model has many potential applications due to the availability of ...non-stressful blood sampling from four arterial and/or venous vascular locations. Samples of blood for biochemical or pharmacological measurements were obtained from the carotid and femoral arteries as well as the pulmonary artery and inferior vena cava. Left ventricular hypertrophy up to 128% of the non-operated control animals was produced at 96 h post-intraluminal aortic coarctation. Inflation of a balloon in the descending aorta increased outflow resistance and resulted in hypertrophy. Hemodynamic parameters of cardiac function were obtained via a Swan-Ganz cardiac output catheter located permanently in the pulmonary artery. Complications observed in the dog model were minimal and mortality did not occur during the experimental period. This animal model employing multiple implanted catheters for blood sampling plus the ability to impose aortic coarctation in the unrestrained animal provides a flexible model system for biochemical and pharmacological research.
1
The pharmacological characteristics of the myocardial adrenoceptor of the mouse have been examined during embryogenesis by measuring ornithine decarboxylase (ODC, EC 4.1.1.17) induction.
2
A four ...fold elevation of ODC activity was observed after isoprenaline (10 mg/kg, s.c), and enzyme activity was increased two to three fold following adrenaline (1 mg/kg, s.c.) or terbutaline given by direct injection to the foetus (10 μg/500 mg).
3
Pretreatment with the β‐adrenoceptor antagonist, propranolol (10 mg/kg), totally blocked the increase in ODC activity.
4
Elevation of myocardial ODC activity was not inhibited by metoprolol, a relatively specific β1‐adrenoceptor antagonist, at a dose of 10 mg/kg.
5
Since the increase in ODC activity was blocked by a β‐adrenoceptor antagonist (propranolol) and enzyme activity was stimulated by terbutaline, a β2‐agonist, we conclude that β2‐adrenoceptors are selectively coupled to the regulation of murine cardiac ODC activity following catecholamine stimulation.
PDF
