The polymorphism -2548 G/A in leptin and severity of Chronic Obstructive Pulmonary Disease

Ye, X.-W.; Xiao, Min; Ye, J.; Zhang, X.-Y.; Xiao, Jun; Feng, Yu; Wen, Fuqiang

doi:10.1111/j.1744-313x.2010.00968.x

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…Leptin, recently implicated in the exacerbation of inflammation in the obese, increases expression of IRAK-1 in macrophages (57) and is known to influence a broad array of TLR signaling, including TLR4, in adipocytes (10). A polymorphism within the leptin promoter region has been identified to be associated with increased circulating leptin levels and worsening severity of COPD (62). It is possible that the mechanism linking atherosclerosis and emphysema is attributed to a persistent systemic inflammation, from multiple different sources, all ultimately acting through the TLR4 signaling pathway with the resultant inflammatory and protease cascade contributing to the development and/or disease progression of both emphysema and atherosclerosis.…”

Section: Discussionmentioning

confidence: 98%

Activation of the TLR4 signaling pathway and abnormal cholesterol efflux lead to emphysema in ApoE-deficient mice

Goldklang

Golovatch

Zelonina

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Smokers with airflow obstruction have an increased risk of atherosclerosis, but the relationship between the pathogenesis of these diseases is not well understood. To determine whether hypercholesterolemia alters lung inflammation and emphysema formation, we examined the lung phenotype of two hypercholesterolemic murine models of atherosclerosis at baseline and on a high-fat diet. Airspace enlargement developed in the lungs of apolipoprotein E-deficient (Apoe(-/-)) mice exposed to a Western-type diet for 10 wk. An elevated number of macrophages and lymphocytes accompanied by an increase in matrix metalloproteinase-9 (MMP-9) activity and MMP-12 expression was observed in the lungs of Apoe(-/-) mice on a Western-type diet. In contrast, low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice did not exhibit lung destruction or inflammatory changes. Most importantly, we revealed augmented expression of the downstream targets of the Toll-like receptor (TLR) pathway, interleukin-1 receptor-associated kinase 1, and granulocyte colony-stimulating factor, in the lungs of Apoe(-/-) mice fed with a Western-type diet. In addition, we demonstrated overexpression of MMP-9 in Apoe(-/-) macrophages treated with TLR4 ligand, augmented with the addition of oxidized LDL, suggesting that emphysema in these mice results from the activation of the TLR pathway secondary to known abnormal cholesterol efflux. Our findings indicate that, in Apoe(-/-) mice fed with an atherogenic diet, abnormal cholesterol efflux leads to increased systemic inflammation with subsequent lung damage and emphysema formation.

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Section: Discussionmentioning

confidence: 98%

Activation of the TLR4 signaling pathway and abnormal cholesterol efflux lead to emphysema in ApoE-deficient mice

Goldklang

Golovatch

Zelonina

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Several single-nucleotide polymorphisms (SNPs) found in the LEP gene may be associated with serum leptin concentration or body mass index (BMI) [14,15,16,17]. Additionally, the LEPR genes have been investigated for gene variants potentially related to the pathophysiology of obesity, T2DM, and its associated complications [18].…”

Section: Introductionmentioning

confidence: 99%

Leptin Gene G2548A Polymorphism among Mongolians with Metabolic Syndrome

et al. 2018

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Metabolic syndrome (MetS) corresponds with multiple risk factors. Many studies have indicated that MetS significantly increases the risk of cardiovascular diseases and type 2 diabetes (T2D). The prevalence of MetS was estimated to be one third of the general Mongolian population in 2015. The purpose of our study was to determine polymorphisms of the LEP (Leptin) and LEPR (Leptin receptor) genes that show susceptibility to MetS and to predict the genetic risk of MetS. We selected 160 cases with MetS and 144 with healthy controls. The G2548A polymorphism of the LEP gene and the A668G (Q223R) polymorphism of the LEPR gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results of the regression analysis showed that the 2548 amino acids (AA) of LEP gene carriers had increased incidences of MetS (OR = 3.23; p = 0.035). Patients with MetS who were 2548A allele carriers had an increased concentration of serum leptin (p = 0.011). Moreover, G2548A of LEP polymorphism was associated with elevated body mass index (BMI) and fasting blood glucose (FBG) in the case group. Our results confirm that the LEP G2548A loci is the independent risk factor of MetS.

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“…In patients with COPD, increases in leptin levels correlate with a proinflammatory state (145). Leptin polymorphisms have also been associated with COPD severity (146). Leptin has been shown to promote a Th17-mediated inflammatory response in lupus-prone mice (147) and to inhibit autophagy in CD4 1 T cells (148).…”

Section: Impact Of Autophagy In the Pathogenesis Of Obesityrelated Lumentioning

confidence: 99%

Autophagy and Obesity-Related Lung Disease

Pabón

Kevin

Choi

2016

Am J Respir Cell Mol Biol

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Obesity-related disease is a significant source of premature death and economic burden globally. It is also a common comorbidity in patients suffering from lung disease, affecting both severity and treatment success. However, this complex association between obesity and the lung is poorly understood. Autophagy is a self-recycling homeostatic process that has been linked to beneficial or deleterious effects, depending on the specific lung disease. Obesity affects autophagy in a tissue-specific manner, activating autophagy in adipocytes and impairing autophagy in hepatocytes, immune cells, and pancreatic β-cells, among others. Obesity is also characterized by chronic low-grade inflammation that can be modulated by the pro- and antiinflammatory effects of the autophagic machinery. Scant evidence exists regarding the impact of autophagy in obesity-related lung diseases, but there are communal pathways that could be related to disease pathogenesis. Important signaling molecules in obesity, including IL-17, leptin, adiponectin, NLRP3 inflammasome, and TLR-4, have been implicated in the pathogenesis of lung disease. These mediators are known to be modulated by autophagy activity. In this perspective, we highlight the recent advances in the understanding of autophagy in obesity-related conditions, as well as the potential mechanisms that can link autophagy and obesity in the pathogenesis of lung disease.

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The polymorphism -2548 G/A in leptin and severity of Chronic Obstructive Pulmonary Disease

Cited by 9 publications

References 31 publications

Activation of the TLR4 signaling pathway and abnormal cholesterol efflux lead to emphysema in ApoE-deficient mice

Activation of the TLR4 signaling pathway and abnormal cholesterol efflux lead to emphysema in ApoE-deficient mice

Leptin Gene G2548A Polymorphism among Mongolians with Metabolic Syndrome

Autophagy and Obesity-Related Lung Disease

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