title: Metabolic Syndrome Is Associated with Increased Oxo-Nitrative Stress and Asthma-Like Changes in Lungs.
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.
authors.affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Vijay Pal
authors.initials: VP
authors.lastname: Singh
authors.affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Rangoli
authors.initials: R
authors.lastname: Aggarwal
authors.affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Suchita
authors.initials: S
authors.lastname: Singh
authors.affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Arpita
authors.initials: A
authors.lastname: Banik
authors.affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Tanveer
authors.initials: T
authors.lastname: Ahmad
authors.affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Bijay Ranjan
authors.initials: BR
authors.lastname: Patnaik
authors.affiliation: National Centre for Laboratory Animal Sciences, National Institute of Nutrition, Tarnaka, Hyderabad, AP, India.
authors.forename: Giridharan
authors.initials: G
authors.lastname: Nappanveettil
authors.affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Kunal Pratap
authors.initials: KP
authors.lastname: Singh
authors.affiliation: Shriram Institute of Industrial Research, University Road, Delhi, India.
authors.forename: Madan Lal
authors.initials: ML
authors.lastname: Aggarwal
authors.affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
authors.affiliation: Centre of Excellence for Translational Research in Asthma and Lung Disease, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Agrawal
mesh_terms: D050154:Adiposity / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001249:Asthma / Q000473:pathology*; D001835:Body Weight; D059305:Diet, High-Fat; D004041:Dietary Fats; D005632:Fructose; D006943:Hyperglycemia / Q000473:pathology; D006946:Hyperinsulinism / Q000473:pathology; D006949:Hyperlipidemias / Q000473:pathology; D008168:Lung / Q000473:pathology*; D008297:Male; D024821:Metabolic Syndrome / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D004041:Dietary Fats; D005632:Fructose; D009569:Nitric Oxide; D001120:Arginine