Leptin and leptin receptor expression in asthma

Bruno, Andreina; Pace, Elisabetta; Chanez, Pascal; Gras, Delphine; Vachier, Isabelle; Chiappara, Giuseppina; Guardia, Maurizio La; Gerbino, Stefania; Profita, Mirella; Gjomarkaj, Mark

doi:10.1016/j.jaci.2009.04.032

Cited by 121 publications

(121 citation statements)

References 40 publications

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“…We found evidence of leptin and leptin receptor expression within airway epithelium. Previous reports have also shown that leptin and leptin receptor are expressed in airway epithelium (24), and bronchial expression of leptin is increased in chronic obstructive pulmonary disease (25,26). Leptin seems to be involved in embryonic lung growth and maturation (27,28), and in fibroproliferative responses in the lung to bleomycin (29).…”

Section: Discussionmentioning

confidence: 95%

Obesity and Asthma

Sideleva¹,

Suratt²,

Black³

et al. 2012

Am J Respir Crit Care Med

299

159

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Rationale: Obesity is a major risk factor for asthma; the reasons for this are poorly understood, although it is thought that inflammatory changes in adipose tissue in obesity could contribute to airway inflammation and airway reactivity in individuals who are obese. Objectives: To determine if inflammation in adipose tissue in obesity is related to late-onset asthma, and associated with increased markers of airway inflammation and reactivity. Methods: We recruited a cohort of obese women with asthma and obese control women. We followed subjects with asthma for 12 months after bariatric surgery. We compared markers in adipose tissue and the airway from subjects with asthma and control subjects, and changes in subjects with asthma over time. Measurements and Main Results: Subjects with asthma had increased macrophage infiltration of visceral adipose tissue (P , 0.01), with increased expression of leptin (P , 0.01) and decreased adiponectin (p , 0.001) when controlled for body mass index. Similar trends were observed in subcutaneous adipose tissue. Airway epithelial cells expressed receptors for leptin and adiponectin, and airway reactivity was significantly related to visceral fat leptin expression (rho ¼ 20.8; P , 0.01). Bronchoalveolar lavage cytokines and cytokine production from alveolar macrophages were similar in subjects with asthma and control subjects at baseline, and tended to increase 12 months after surgery. Conclusions: Obesity is associated with increased markers of inflammation in serum and adipose tissue, and yet decreased airway inflammation in obese people with asthma; these patterns reverse with bariatric surgery. Leptin and other adipokines may be important mediators of airway disease in obesity through direct effects on the airway rather than by enhancing airway inflammation.

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Section: Discussionmentioning

confidence: 95%

Obesity and Asthma

Sideleva¹,

Suratt²,

Black³

et al. 2012

Am J Respir Crit Care Med

299

159

View full text Add to dashboard Cite

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“…We show that elevated leptin increases the odds of abnormal FEV 1 by more than twofold after adjustment for BMI. A role for this adipocyte-derived cytokine in impaired lung function is plausible because leptin has receptors in the lung and is increased in inflammation (41,47,48). The triglycerides and HDL mechanism underlying the association of leptin with lung function is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Syndrome Biomarkers Predict Lung Function Impairment

Naveed

Weiden

Kwon

et al. 2012

Am J Respir Crit Care Med

113

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Rationale:Cross-sectional studies demonstrate an association between metabolic syndrome and impaired lung function. Objectives: To define if metabolic syndrome biomarkers are risk factors for loss of lung function after irritant exposure. Methods: A nested case-control study of Fire Department of New York personnel with normal pre-September 11th FEV 1 and who presented for subspecialty pulmonary evaluation before March 10, 2008. We correlated metabolic syndrome biomarkers obtained within 6 months of World Trade Center dust exposure with subsequent FEV 1 . FEV 1 at subspecialty pulmonary evaluation within 6.5 years defined disease status; cases had FEV 1 less than lower limit of normal, whereas control subjects had FEV 1 greater than or equal to lower limit of normal. Measurements and Main Results: Clinical data and serum sampled at the first monitoring examination within 6 months of September 11, 2001, assessed body mass index, heart rate, serum glucose, triglycerides and high-density lipoprotein (HDL), leptin, pancreatic polypeptide, and amylin. Cases and control subjects had significant differences in HDL less than 40 mg/dl with triglycerides greater than or equal to 150 mg/dl, heart rate greater than or equal to 66 bpm, and leptin greater than or equal to 10,300 pg/ml. Each increased the odds of abnormal FEV 1 at pulmonary evaluation by more than twofold, whereas amylin greater than or equal to 116 pg/ml decreased the odds by 84%, in a multibiomarker model adjusting for age, race, body mass index, and World Trade Center arrival time. This model had a sensitivity of 41%, a specificity of 86%, and a receiver operating characteristic area under the curve of 0.77. Conclusions: Abnormal triglycerides and HDL and elevated heart rate and leptin are independent risk factors of greater susceptibility to lung function impairment after September 11, 2001, whereas elevated amylin is protective. Metabolic biomarkers are predictors of lung disease, and may be useful for assessing risk of impaired lung function in response to particulate inhalation.

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“…Single or repeated injections of glucocorticoids were also shown to elevate rat plasma leptin in a dose-dependent manner [12]. On the other hand, leptin receptor expression was decreased in vitro in human bronchial epithelial cells by transforming growth factor b1 (TGF-b1) [13]. Despite these results, no mechanism of leptin expression has been proposed.…”

mentioning

confidence: 99%

Differential Signalling Through ALK-1 and ALK-5 Regulates Leptin Expression in Mesenchymal Stem Cells

Zeddou¹,

Relić

Malaise

et al. 2012

Stem Cells and Development

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Leptin plays a central role in maintaining energy balance, with multiple other systemic effects. Despite leptin importance in peripheral regulation of mesenchymal stem cells (MSC) differentiation, little is known about its expression mechanism. Leptin is often described as adipokine, while it is expressed by other cell types. We have recently shown an in vitro leptin expression, enhanced by glucocorticoids in synovial fibroblasts (SVF). Here, we investigated leptin expression in MSC from bone marrow (BM-MSC) and umbilical cord matrix (UMSC). Results showed that BM-MSC, but not UMSC, expressed leptin that was strongly enhanced by glucocorticoids. Transforming growth factor b1 (TGF-b1) markedly inhibited the endogenous-and glucocorticoid-induced leptin expression in BM-MSC. Since TGF-b1 was shown to signal via ALK-5-Smad2/3 and/or ALK-1-Smad1/5 pathways, we analyzed the expression of proteins from both pathways. In BM-MSC, TGF-b1 increased phosphorylated Smad2 (p-Smad2) expression, while ALK-5 inhibitor (SB431542) induced leptin expression and significantly restored TGF-b1-induced leptin inhibition. In addition, both prednisolone and SB431542 increased p-Smad1/5 expression. These results suggested the ALK-5-Smad2 pathway as an inhibitor of leptin expression, while ALK-1-Smad1/5 as an activator. Indeed, Smad1 expression silencing induced leptin expression inhibition. Furthermore, prednisolone enhanced the expression of TGF-bRII while decreasing p-Smad2 in BM-MSC and SVF but not in UMSC. In vitro differentiation revealed differential osteogenic potential in SVF, BM-MSC, and UMSC that was correlated to their leptin expression potential. Our results suggest that ALK-1/ALK-5 balance regulates leptin expression in MSC. It also underlines UMSC as leptin nonproducer MSC for cell therapy protocols where leptin expression is not suitable.

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Leptin and leptin receptor expression in asthma

Abstract: Decreased expression of leptin/leptin receptor characterizes severe asthma and is associated with airway remodeling features.

Cited by 121 publications

References 40 publications

Obesity and Asthma

Obesity and Asthma

Metabolic Syndrome Biomarkers Predict Lung Function Impairment

Differential Signalling Through ALK-1 and ALK-5 Regulates Leptin Expression in Mesenchymal Stem Cells

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