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

PLoS One. 2015 Jun 22;10(6):e0129850. doi: 10.1371/journal.pone.0129850. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / physiology
  • Animals
  • Arginine / metabolism
  • Asthma / pathology*
  • Body Weight
  • Diet, High-Fat
  • Dietary Fats
  • Fructose
  • Hyperglycemia / pathology
  • Hyperinsulinism / pathology
  • Hyperlipidemias / pathology
  • Lung / pathology*
  • Male
  • Metabolic Syndrome / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism
  • Obesity / pathology*
  • Oxidative Stress / physiology*

Substances

  • Dietary Fats
  • Fructose
  • Nitric Oxide
  • Arginine

Grant support

Funding was provided by the Lady Tata Memorial Trust, CSIR (Council of Scientific and Industrial Research) MLP (Mega Laboratory Project) 5502 & BSC (Biological Science Cluster) 0403 projects, the DST (Department of Science and Technology) Swarnjayanti awards for the financial support and ICMR (Indian Council of Medical Research) for scholarship of Suchita Singh. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.