leptin and Idiopathic-Pulmonary-Fibrosis

The causal relationships between circulating adipokines and idiopathic pulmonary fibrosis (IPF) are yet to be established. We performed a two-sample Mendelian randomization (MR) study to investigate the causal roles of adipokines on IPF risk.. We analyzed the summary data from genome-wide association studies (GWAS), including adiponectin, leptin, resistin and monocyte chemoattractant protein-1 (MCP-1) and IPF. The inverse-variance weighted (IVW) method was considered as the major method and the MR-Egger, weighted median, simple mode and weighted mode were utilized as complementary methods. We also performed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis.. The selected number of single nucleotide polymorphisms (SNPs) was 13 for adiponectin, 6 for leptin,12 for resistin, and 6 for MCP-1, respectively. The results showed a causal effect of the circulating adiponectin levels on the risk of IPF (OR 0.645, 95% CI 0.457-0.911, P = 0.013). However, we did not observe significant associations of genetic changes in serum leptin (OR 1.018, 95% CI 0.442-2.346, P = 0.967), resistin (OR 1.002, 95% CI 0.712-1.408, P = 0.993), and MCP-1 (OR 1.358, 95% CI 0.891-2.068, P = 0.155) with risk of developing IPF. There was no evidence of heterogeneity or horizontal pleiotropy. The sensitivity analyses confirmed that our results were stable and reliable.. The increase in serum adiponectin was associated causally with a decreased risk of developing IPF. There is no evidence to support a causal association between leptin, resistin or MCP-1 with risk of IPF. Further studies are needed to confirm our findings.

Topics: Adipokines; Adiponectin; Genome-Wide Association Study; Humans; Idiopathic Pulmonary Fibrosis; Leptin; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Resistin

Adipokines (APN) are mainly secreted by adipocytes, macrophages and various other cells, along with their role in the regulation and mediation of inflammatory responses. APN is almost exclusively synthesized by adipocytes and regulated by peroxisome proliferator-activated receptor γ (PPARγ) that is involved in the epithelial-mesenchymal transition, linked lung fibrosis. Leptin is involved in acute lung injury with a role in lung fibrogenesis. Little is known about the relationship between APN/leptin and idiopathic pulmonary fibrosis (IPF) and the few studies available in the literature used ELISA to detect these lipid mediators. Our study is also the first to measure adipokines by the new multiplex assay and for the first time were performed in bronchoalveolar lavage (BAL) from IPF patients. This preliminary study suggests that APN levels in serum could be useful for predicting the prognosis of IPF, as they are inversely correlated with DLco percentages and BMI. Moreover, this first analysis of APN in BAL from IPF patients by a new method demonstrated an inverse correlation between these levels and BMI values and a direct correlation with eosinophil percentages, both of which are negative prognostic factors of IPF.

Topics: Adiponectin; Aged; Biological Assay; Body Mass Index; Bronchoalveolar Lavage Fluid; Female; Humans; Idiopathic Pulmonary Fibrosis; Leptin; Male; Middle Aged

Topics: Acute Disease; Adiponectin; Aged; Aged, 80 and over; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Humans; Idiopathic Pulmonary Fibrosis; Leptin; Male; Middle Aged; Retrospective Studies

Background. The natural history of idiopathic pulmonary fibrosis (IPF) is very complex and unpredictable. Some patients will experience acute exacerbation (AE) and fatal outcomes. Methods. The study included 30 AE-IPF patients, 32 stable IPF (S-IPF) patients, and 12 healthy controls. We measured the plasma concentrations of leptin and KL-6. Simple correlation was used to assess associations between leptin and other variables. Plasma leptin levels were compared between AE-IPF and S-IPF subjects, decedents, and survivors. Kaplan-Meier curves were used to display survival and Cox proportional hazards regression was used to examine risk factors for survival. Results. In subjects with AE-IPF, plasma leptin was significantly greater than in subjects with S-IPF (p = 0.0003) or healthy controls (p < 0.0001). Plasma leptin was correlated with BMI, KL-6, LDH, CRP, and PaO2/FiO2 (p = 0.007; p = 0.005; p = 0.003; p = 0.033; and p = 0.032, resp.). Plasma leptin was significantly greater in 33 decedents than in the 23 survivors (p = 0.007). Multivariate Cox regression analysis showed leptin (>13.79 ng/mL) was an independent predictor of survival (p = 0.004). Conclusions. Leptin could be a promising plasma biomarker of AE-IPF occurrence and predictor of survival in IPF patients.

Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Female; Humans; Idiopathic Pulmonary Fibrosis; Kaplan-Meier Estimate; Leptin; Male; Middle Aged; Mucin-1; Proportional Hazards Models