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Background: The mechanisms of fat mass (FM) loss in cystic fibrosis (CF) are poorly understood but could represent complex pathways involving dysregulation of appetite-modulating peptides and an amplified inflammatory response. Nesfatin-1 is a newly described peptide that decreases food intake and FM but has not been studied in CF. Objectives: We hypothesized that changes in the appetite-suppressing hormone nesfatin-1 would be physiological, and levels would be lower in advanced CF patients with lower FM compared to those with milder disease and healthy controls. We determined the levels of the cytokines TNF-α, IL-1β, and IL-6 as they have been associated with weight loss in disease states. Methods: Fifty-four adult CF subjects, i.e. 17 with severe, 22 with moderate, and 15 with mild disease, as well as 18 controls were recruited. PFT and body composition analysis (via bioelectrical impedance) were performed. Nesfatin-1 and cytokine levels were determined by ELISA. Results: Contrary to our proposed hypothesis, nesfatin-1 levels were highest in CF patients with severe disease and the lowest FM. A significant negative correlation between nesfatin-1 levels and FM was found only in the severe CF group (r = -0.7, p = 0.003). In forward stepwise regression analysis, only FM was significantly associated with nesfatin-1 levels. Levels of TNF-α and IL-6 were elevated in the severe CF group, but there was no association with either FM or nesfatin-1. Conclusion: In advanced CF and low FM, nesfatin-1 plasma levels are significantly increased and inversely correlated with the FM. Our results further suggest that nesfatin-1 exerts its effects independently of TNF-α or IL-6. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Weight loss in cystic fibrosis (CF) may be associated with altered levels of appetite stimulating peptide ghrelin and the appetite decreasing peptide leptin. However, prior data on leptin in CF are conflicting, while the data on ghrelin are scarce. We hypothesized that weight loss in CF is associated with low levels ghrelin and elevated levels of leptin. Methods: Plasma ghrelin, leptin, TNF-α, IL-1 and IL-6, BMI, fat free mass (FFM), fat mass (FM) were measured in 74 CF adults and 20 controls. CF subjects were divided into 3 groups based on lung disease: mild (n =19), moderate (n =30) and severe (n =25). Results: Severe CF patients (% predicted FEV1 27±7; median BMI 21 kg/m2) had significantly elevated ghrelin and decreased leptin compared to controls and other CF subjects. Ghrelin correlated (r value, p value) with BMI (−0.35,<0.001), FFM (−0.22,<0.05), FM (−0.41,<0.0001), FEV1 (−0.62,<0.001), TNF-α (0.51,<0.0001), IL-1 (0.56,<0.0001), and IL-6 (0.33,<0.01). Leptin correlated (r value, p value) with BMI (0.40,<0.0001), FM (0.56,<0.0001), FEV1 (0.34,<0.05), IL-1 (−0.51,<0.05) and TNF-α (−0.43,<0.0001). BMI and FEV1 were independent predictors of ghrelin (−0.35,<0.05;−0.59,<0.001). FM was a predictor of leptin (0.56,<0.0001). Cytokines were elevated only in severe CF (severe CF vs. controls, pg/ml): TNF-α (3.4±0.6 vs. 1.2±0.4), IL-1 (3.5±1 vs. 0.2±0.1), IL-6 (17.4±4 vs. 2.4±2). Conclusions: Elevated ghrelin and decreased leptin levels are a consequence rather than a cause of weight loss in advanced CF. [Copyright &y& Elsevier]