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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

Increased baseline resistance and decreased exhaled NO in mice with metabolic syndrome.(A-B) Baseline lung resistance (R) and elastance (E) in anesthetized and ventilated control, high fat (HFA) and high fructose (HFR) diet fed mice (Mean ± SE, n = 12 per group, two independent sets of experiments). (C) Non-invasively measured exhaled NO of control, HFA and HFR mice (n = 6 per group). All data are Mean ± SE. n = 6 mice in each group *Denotes statistically significant differences (p<0.05) vs control.
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pone.0129850.g002: Increased baseline resistance and decreased exhaled NO in mice with metabolic syndrome.(A-B) Baseline lung resistance (R) and elastance (E) in anesthetized and ventilated control, high fat (HFA) and high fructose (HFR) diet fed mice (Mean ± SE, n = 12 per group, two independent sets of experiments). (C) Non-invasively measured exhaled NO of control, HFA and HFR mice (n = 6 per group). All data are Mean ± SE. n = 6 mice in each group *Denotes statistically significant differences (p<0.05) vs control.

Mentions: Baseline lung resistance was found to be increased in HFR group, compared to CN mice. Maximal lung resistance after methacholine challenge was increased in both HFR and HFA mice and was maximal in HFA group (Fig 2A). Elastance was similar at baseline but went up significantly in HFA mice during methacholine challenge (Fig 2B), presumably due to greater peripheral airway closure in obese mice at identical PEEP settings. Since reduced exhaled NO has been previously observed in obese human asthmatics [22], we further measured exhaled NO (ENO) in a subset of each group. Significantly lower levels of ENO were found in HFA and HFR groups compared to CN (Fig 2C).


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)

Increased baseline resistance and decreased exhaled NO in mice with metabolic syndrome.(A-B) Baseline lung resistance (R) and elastance (E) in anesthetized and ventilated control, high fat (HFA) and high fructose (HFR) diet fed mice (Mean ± SE, n = 12 per group, two independent sets of experiments). (C) Non-invasively measured exhaled NO of control, HFA and HFR mice (n = 6 per group). All data are Mean ± SE. n = 6 mice in each group *Denotes statistically significant differences (p<0.05) vs control.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4476757&req=5

pone.0129850.g002: Increased baseline resistance and decreased exhaled NO in mice with metabolic syndrome.(A-B) Baseline lung resistance (R) and elastance (E) in anesthetized and ventilated control, high fat (HFA) and high fructose (HFR) diet fed mice (Mean ± SE, n = 12 per group, two independent sets of experiments). (C) Non-invasively measured exhaled NO of control, HFA and HFR mice (n = 6 per group). All data are Mean ± SE. n = 6 mice in each group *Denotes statistically significant differences (p<0.05) vs control.
Mentions: Baseline lung resistance was found to be increased in HFR group, compared to CN mice. Maximal lung resistance after methacholine challenge was increased in both HFR and HFA mice and was maximal in HFA group (Fig 2A). Elastance was similar at baseline but went up significantly in HFA mice during methacholine challenge (Fig 2B), presumably due to greater peripheral airway closure in obese mice at identical PEEP settings. Since reduced exhaled NO has been previously observed in obese human asthmatics [22], we further measured exhaled NO (ENO) in a subset of each group. Significantly lower levels of ENO were found in HFA and HFR groups compared to CN (Fig 2C).

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