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Metabolic Syndrome Is Associated with Increased Oxo-Nitrative Stress and Asthma-Like Changes in Lungs.

Singh VP, Aggarwal R, Singh S, Banik A, Ahmad T, Patnaik BR, Nappanveettil G, Singh KP, Aggarwal ML, Ghosh B, Agrawal A - PLoS ONE (2015)

Bottom Line: Since high-sugar diets can induce MetS, without necessarily causing obesity, studies of their effect on arginine/NO metabolism and airway function could clarify this aspect.Exhaled NO was reduced in both these groups.This reduction in exhaled NO correlated with reduced arginine bioavailability in lungs.

View Article: PubMed Central - PubMed

Affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.

ABSTRACT
Epidemiological studies have shown an increased obesity-related risk of asthma. In support, obese mice develop airway hyperresponsiveness (AHR). However, it remains unclear whether the increased risk is a consequence of obesity, adipogenic diet, or the metabolic syndrome (MetS). Altered L-arginine and nitric oxide (NO) metabolism is a common feature between asthma and metabolic syndrome that appears independent of body mass. Increased asthma risk resulting from such metabolic changes would have important consequences in global health. Since high-sugar diets can induce MetS, without necessarily causing obesity, studies of their effect on arginine/NO metabolism and airway function could clarify this aspect. We investigated whether normal-weight mice with MetS, due to high-fructose diet, had dysfunctional arginine/NO metabolism and features of asthma. Mice were fed chow-diet, high-fat-diet, or high-fructose-diet for 18 weeks. Only the high-fat-diet group developed obesity or adiposity. Hyperinsulinemia, hyperglycaemia, and hyperlipidaemia were common to both high-fat-diet and high-fructose-diet groups and the high-fructose-diet group additionally developed hypertension. At 18 weeks, airway hyperresponsiveness (AHR) could be seen in obese high-fat-diet mice as well as non-obese high-fructose-diet mice, when compared to standard chow-diet mice. No inflammatory cell infiltrate or goblet cell metaplasia was seen in either high-fat-diet or high-fructose-diet mice. Exhaled NO was reduced in both these groups. This reduction in exhaled NO correlated with reduced arginine bioavailability in lungs. In summary, mice with normal weight but metabolic obesity show reduced arginine bioavailability, reduced NO production, and asthma-like features. Reduced NO related bronchodilation and increased oxo-nitrosative stress may contribute to the pathogenesis.

No MeSH data available.


Related in: MedlinePlus

Lack of cellular inflammation in lungs of mice with metabolic syndrome.(A) Lung sections were stained with haematoxylin and eosin to estimate airway inflammation. (B) Inflammation score of the lungs was evaluated by experimentally blind experts and shown as perivascular (PV), peribronchial (PB) and Total (sum of both PV and PB). (Representative images are shown from each group. All photographs are at 10X magnification. Scale bar = 100μm.
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pone.0129850.g006: Lack of cellular inflammation in lungs of mice with metabolic syndrome.(A) Lung sections were stained with haematoxylin and eosin to estimate airway inflammation. (B) Inflammation score of the lungs was evaluated by experimentally blind experts and shown as perivascular (PV), peribronchial (PB) and Total (sum of both PV and PB). (Representative images are shown from each group. All photographs are at 10X magnification. Scale bar = 100μm.

Mentions: To determine the effects of increased oxo-nitrative stress and other metabolic changes on lung structure, we performed histological studies. Cellular infiltration was measured with Haematoxylin & Eosin staining. Inflammatory cells did not appear to be significantly different between groups (Fig 6A) and this was also confirmed by a semi-quantitative inflammation score of the lungs (Fig 6B). Sub epithelial collagen, as judged by Masson Trichrome stain, appeared to be increased in HFA and HFR mice (S3A Fig). However, quantitative morphometry of the sub-epithelial collagen content showed high variability and the differences between groups were not significant by ANOVA (S3B Fig). However, the pooled MetS groups (HFA and HFR) had significantly greater sub-epithelial collagen content than control mice (one-tailed t-test, p = 0.0256).


Metabolic Syndrome Is Associated with Increased Oxo-Nitrative Stress and Asthma-Like Changes in Lungs.

Singh VP, Aggarwal R, Singh S, Banik A, Ahmad T, Patnaik BR, Nappanveettil G, Singh KP, Aggarwal ML, Ghosh B, Agrawal A - PLoS ONE (2015)

Lack of cellular inflammation in lungs of mice with metabolic syndrome.(A) Lung sections were stained with haematoxylin and eosin to estimate airway inflammation. (B) Inflammation score of the lungs was evaluated by experimentally blind experts and shown as perivascular (PV), peribronchial (PB) and Total (sum of both PV and PB). (Representative images are shown from each group. All photographs are at 10X magnification. Scale bar = 100μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476757&req=5

pone.0129850.g006: Lack of cellular inflammation in lungs of mice with metabolic syndrome.(A) Lung sections were stained with haematoxylin and eosin to estimate airway inflammation. (B) Inflammation score of the lungs was evaluated by experimentally blind experts and shown as perivascular (PV), peribronchial (PB) and Total (sum of both PV and PB). (Representative images are shown from each group. All photographs are at 10X magnification. Scale bar = 100μm.
Mentions: To determine the effects of increased oxo-nitrative stress and other metabolic changes on lung structure, we performed histological studies. Cellular infiltration was measured with Haematoxylin & Eosin staining. Inflammatory cells did not appear to be significantly different between groups (Fig 6A) and this was also confirmed by a semi-quantitative inflammation score of the lungs (Fig 6B). Sub epithelial collagen, as judged by Masson Trichrome stain, appeared to be increased in HFA and HFR mice (S3A Fig). However, quantitative morphometry of the sub-epithelial collagen content showed high variability and the differences between groups were not significant by ANOVA (S3B Fig). However, the pooled MetS groups (HFA and HFR) had significantly greater sub-epithelial collagen content than control mice (one-tailed t-test, p = 0.0256).

Bottom Line: Since high-sugar diets can induce MetS, without necessarily causing obesity, studies of their effect on arginine/NO metabolism and airway function could clarify this aspect.Exhaled NO was reduced in both these groups.This reduction in exhaled NO correlated with reduced arginine bioavailability in lungs.

View Article: PubMed Central - PubMed

Affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.

ABSTRACT
Epidemiological studies have shown an increased obesity-related risk of asthma. In support, obese mice develop airway hyperresponsiveness (AHR). However, it remains unclear whether the increased risk is a consequence of obesity, adipogenic diet, or the metabolic syndrome (MetS). Altered L-arginine and nitric oxide (NO) metabolism is a common feature between asthma and metabolic syndrome that appears independent of body mass. Increased asthma risk resulting from such metabolic changes would have important consequences in global health. Since high-sugar diets can induce MetS, without necessarily causing obesity, studies of their effect on arginine/NO metabolism and airway function could clarify this aspect. We investigated whether normal-weight mice with MetS, due to high-fructose diet, had dysfunctional arginine/NO metabolism and features of asthma. Mice were fed chow-diet, high-fat-diet, or high-fructose-diet for 18 weeks. Only the high-fat-diet group developed obesity or adiposity. Hyperinsulinemia, hyperglycaemia, and hyperlipidaemia were common to both high-fat-diet and high-fructose-diet groups and the high-fructose-diet group additionally developed hypertension. At 18 weeks, airway hyperresponsiveness (AHR) could be seen in obese high-fat-diet mice as well as non-obese high-fructose-diet mice, when compared to standard chow-diet mice. No inflammatory cell infiltrate or goblet cell metaplasia was seen in either high-fat-diet or high-fructose-diet mice. Exhaled NO was reduced in both these groups. This reduction in exhaled NO correlated with reduced arginine bioavailability in lungs. In summary, mice with normal weight but metabolic obesity show reduced arginine bioavailability, reduced NO production, and asthma-like features. Reduced NO related bronchodilation and increased oxo-nitrosative stress may contribute to the pathogenesis.

No MeSH data available.


Related in: MedlinePlus