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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

Induction of Inducible Nitric oxide synthase (iNOS) in lungs of mice with metabolic syndrome.(A) Western blot analysis of eNOS. (B) Western blot analysis of iNOS (C) Densitometry of eNOS (D) Densitometry of iNOS (E) Immunohistochemistry of iNOS. Brown colour indicates the positive expressions. HFA and HFR diet fed mice showed high expression of iNOS as compared to Control mice. Representative images are shown from each group. All photographs are at 10X magnification. Scale bar = 100μm. (F) Quantitative analysis for iNOS done using ImageJ software showed significant increase in its expression in HFA and HFR mice as compared to CN.*Denotes statistically significant differences (P<0.05) vs. Control.
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pone.0129850.g004: Induction of Inducible Nitric oxide synthase (iNOS) in lungs of mice with metabolic syndrome.(A) Western blot analysis of eNOS. (B) Western blot analysis of iNOS (C) Densitometry of eNOS (D) Densitometry of iNOS (E) Immunohistochemistry of iNOS. Brown colour indicates the positive expressions. HFA and HFR diet fed mice showed high expression of iNOS as compared to Control mice. Representative images are shown from each group. All photographs are at 10X magnification. Scale bar = 100μm. (F) Quantitative analysis for iNOS done using ImageJ software showed significant increase in its expression in HFA and HFR mice as compared to CN.*Denotes statistically significant differences (P<0.05) vs. Control.

Mentions: We further investigated whether enzymes that regulate arginine metabolism and NO production (arginase-1, eNOS, and iNOS) were differently expressed in lungs of mice with MetS. No major change was seen in eNOS expression (Fig 4A and 4C) and iNOS expression was somewhat increased (Fig 4B–4F, S2 Fig), suggesting that the reduction in NO production was related to functional inhibition of the NOS pathway and not loss of NOS enzymes. In HFA group, lung arginase-1 expression was markedly increased consistent with lower L-arginine levels in lungs of such mice (Fig 5A–5C) (see above). Minimal increase in Arginase-1 was also seen in HFR (Fig 5D, S1 Fig).


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)

Induction of Inducible Nitric oxide synthase (iNOS) in lungs of mice with metabolic syndrome.(A) Western blot analysis of eNOS. (B) Western blot analysis of iNOS (C) Densitometry of eNOS (D) Densitometry of iNOS (E) Immunohistochemistry of iNOS. Brown colour indicates the positive expressions. HFA and HFR diet fed mice showed high expression of iNOS as compared to Control mice. Representative images are shown from each group. All photographs are at 10X magnification. Scale bar = 100μm. (F) Quantitative analysis for iNOS done using ImageJ software showed significant increase in its expression in HFA and HFR mice as compared to CN.*Denotes statistically significant differences (P<0.05) vs. Control.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0129850.g004: Induction of Inducible Nitric oxide synthase (iNOS) in lungs of mice with metabolic syndrome.(A) Western blot analysis of eNOS. (B) Western blot analysis of iNOS (C) Densitometry of eNOS (D) Densitometry of iNOS (E) Immunohistochemistry of iNOS. Brown colour indicates the positive expressions. HFA and HFR diet fed mice showed high expression of iNOS as compared to Control mice. Representative images are shown from each group. All photographs are at 10X magnification. Scale bar = 100μm. (F) Quantitative analysis for iNOS done using ImageJ software showed significant increase in its expression in HFA and HFR mice as compared to CN.*Denotes statistically significant differences (P<0.05) vs. Control.
Mentions: We further investigated whether enzymes that regulate arginine metabolism and NO production (arginase-1, eNOS, and iNOS) were differently expressed in lungs of mice with MetS. No major change was seen in eNOS expression (Fig 4A and 4C) and iNOS expression was somewhat increased (Fig 4B–4F, S2 Fig), suggesting that the reduction in NO production was related to functional inhibition of the NOS pathway and not loss of NOS enzymes. In HFA group, lung arginase-1 expression was markedly increased consistent with lower L-arginine levels in lungs of such mice (Fig 5A–5C) (see above). Minimal increase in Arginase-1 was also seen in HFR (Fig 5D, S1 Fig).

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