Date of Award
Doctor of Philosophy
Michael B. Zemel
Jay Whelan, Dallas Donohoe, Joseph Bartges
Over the past several decades the prevalence of obesity and asthma have increased in a parallel fashion. Recent studies reported a positive relationship between the two disorders that may in fact be causal. Although the link between obesity and asthma has become widely recognized, the underlying pathophysiological connection is not elucidated. Increased markers of inflammatory and oxidative stress are present in obesity and asthma suggesting the link is immunological. The systemic inflammation observed in obesity may potentially initiate adverse affects in the airways. Previous studies have shown that consumption of dairy foods (rich in calcium and leucine) suppress 1,25-dihydroxycholecalciferol (calcitriol) resulting in decreased inflammatory stress associated with excess adiposity. Additionally, adipocyte leucine treatment was reported to decrease pro-inflammatory TNFα and increase anti-inflammatory adiponectin cytokines, which have been implicated in asthmatic disease. Consequently, we sought to determine if correcting the imbalance of adipocyte inflammatory cytokine secretion via calcium and leucine treatment would have a functional effect on airway inflammation. We demonstrated that conditioned medium collected adipocytes (ACM) treated with leucine for 48hrs significantly reduced monocyte-airway smooth muscle adhesion, lung endothelial cell ICAM-1 adhesion molecule expression, and polymorphonuclear (PMN) cell CD11b expression in vitro compared to control, while calcitriol exerted the opposite effects. Furthermore, these findings were extended to an established murine model of asthma. Female BALB/c mice were sensitized and challenged with chicken egg albumin (OVA) to induce airway inflammation. Animals were fed a high fat diet with no supplementation, high calcium (1.2%), leucine (200% normal levels), or a diet with a combination of calcium (1.2%) and leucine (200% normal levels). We found that the combined high calcium and leucine supplemented high fat diet animals had significantly less eosinophils in collected bronchoalveolar lavage fluid (BALF) compared to control diet mice. These data suggest that calcium and leucine may have potential therapeutic affects on obesity associated airway inflammation.
Brown, Patricia Louise, "Calcium and Leucine Modulation of Airway Inflammation. " PhD diss., University of Tennessee, 2014.