Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis

Imoto, Yoshimasa; Ueki, Shigeharu; Kato, Yoshio; Yoshida, Kanako; Morikawa, Taiyo; Kimura, Yukihiro; Kidoguchi, Masanori; Tsutsumiuchi, Toshiki; Koyama, Keisuke; Adachi, Naoto; Ito, Yatsuji; Ogi, Kazuhiro; Sakashita, Masafumi; Yamada, Tetsuji; Schleimer, Robert P.; Takabayashi, Tetsuji; Fujieda, Shigeharu

doi:10.3389/fphar.2021.793607

Cited by 9 publications

(11 citation statements)

References 66 publications

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“…Leptin, a proinflammatory adipokine predominantly released from adipocytes, plays a key role in the regulation of food intake, body weight and energy metabolism. Several recent studies have reported that serum leptin levels increase in various inflammatory airway diseases, including COPD, asthma, AR, CRS, and nasal polyposis [1,2,5,[23][24][25]. Leptin receptors are expressed in bronchial epithelial cells, airway immune cells, and nasal epithelial cells [1][2][3].…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Downregulates Lipopolysaccharide/ Leptin-Induced MUC5AC Expression in Human Nasal Epithelial Cells

Choi

Bae

et al. 2023

Clin Exp Otorhinolaryngol

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Objectives. Obesity is a known risk factor for various diseases by inducing chronic low-grade systemic inflammation in the human body. In recent studies, various otorhinolaryngological diseases have also been associated with obesity. In particular, inflammatory sinonasal diseases have been found to be strongly associated with obesity-related proinflammatory mediators. Many studies have been conducted to identify therapeutic agents for controlling obesity-related inflammatory airway diseases. Ghrelin, an endogenous peptide from the stomach, has anti-inflammatory and antioxidative effects in a wide range of tissues. However, the effect of ghrelin on the regulation of mucus secretion has not yet been studied in the human nasal mucosa. Therefore, we investigated the effects of ghrelin on lipopolysaccharide (LPS)/leptin-mediated MUC5AC expression and mechanisms involved in human nasal epithelial cells (HNEpCs).Methods. In HNEpCs, the effect and signaling pathways of ghrelin on LPS/leptin-induced MUC5AC expression were examined using reverse transcription polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassay, western blotting and immunofluorescence staining.Results. Growth hormone secretagogue receptor 1a (GHSR1a) was expressed in the HNEpCs. Ghrelin down-regulated LPS/leptin-induced MUC5AC expression, which was abolished by D-Lys-3-growth hormone-releasing peptide 6 (D-Lys-3-GHRP-6). Ghrelin significantly inhibits LPS/leptin-activated extracellular signal related kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs). These ghrelin-mediated changes in MAPK activation were abolished by D-Lys-3-GHRP-6. These results showed that ghrelin inhibits LPS/leptin-induced MUC5AC overexpression by modulating the ERK1/2 and p38 MAPK pathways in HNEpCs.Conclusions. These findings suggest that ghrelin is a potential therapeutic agent for treating obesity-related inflammatory sinonasal diseases.

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Section: Discussionmentioning

confidence: 99%

Ghrelin Downregulates Lipopolysaccharide/ Leptin-Induced MUC5AC Expression in Human Nasal Epithelial Cells

Choi

Bae

et al. 2023

Clin Exp Otorhinolaryngol

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“…This may indicate leptin plays a role in the disease process of CRSwNP. Furthermore, Imoto et al, a study not included in the meta‐analysis due to missing data, observed that both eosinophilic CRS and noneosinophilic CRS patients had higher average serum leptin levels compared to healthy control patients without significant differences in BMI between cohorts 39 . Additionally, Song et al identified increased expression of leptin receptors in nasal polyps of patients with CRSwNP compared to the normal mucosa of healthy controls 40 .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, Imoto et al, a study not included in the meta-analysis due to missing data, observed that both eosinophilic CRS and noneosinophilic CRS patients had higher average serum leptin levels compared to healthy control patients without significant differences in BMI between cohorts. 39 Additionally, Song et al identified increased expression of leptin receptors in nasal polyps of patients with CRSwNP compared to the normal mucosa of healthy controls. 40 Taken together, leptin may play a role in CRS, and additional research is needed to investigate these associations to gain a better understanding of the influence of leptin on the inflammatory profile of CRS patients.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Association of Obesity and Chronic Rhinosinusitis: A Systematic Review and Meta‐analysis

Hoying,

Miller,

Tanzo

et al. 2023

Otolaryngol.--head neck surg.

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ObjectiveThe aim of this Meta‐analysis and systematic review was to perform a comprehensive assessment of the association of chronic rhinosinusitis (CRS) with overweight/obesity, leptin hormone, and its associated metabolic dysregulation.Data SourcesOvid MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, were searched for studies from 1946 to October 2022, using predefined syntax.Review MethodsOutcome data for the meta‐analysis were extracted on odds ratios (OR) of CRS prevalence based on the presence of overweight/obesity and mean serum leptin levels. A Meta‐analysis was performed using the DerSimonian‐Laird estimator to pool extracted data by the generalized inverse variance approach. Random effect models were utilized due to the small sample size. A qualitative synthesis was performed on articles that did not meet the inclusion criteria for the Meta‐analysis.ResultsThirty‐six studies met the systematic review inclusion criteria out of 1113 articles screened. A total of 6 studies were included in the pooled Meta‐analysis of the various outcome variables. Our pooled meta‐analysis observed a positive association between overweight/obesity and the prevalence of CRS (OR = 1.33, 95% confidence interval [CI]: 1.17‐1.51). The pooled ratio of the means analysis of the mean serum leptin levels between CRS with nasal polyposis and control patients was 2.21 (95% CI: 1.45; 3.36).ConclusionOur pooled Meta‐analysis indicates a positive association between overweight/obesity and CRS. Future prospective studies are needed to explore the association between CRS and obesity with an understanding of potential confounding comorbidities, including studies focused on assessing the underlying immunologic mechanism of this association.

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“…Although FESS is an effective treatment that rapidly alleviates clinical symptoms, a large proportion of CRSwNP patients require repeated surgery due to recurrence, particularly for those with a higher degree of tissue eosinophil infiltration [35][36][37]. Thereby, identifying biomarkers to early predict the recurrence of CRSwNP is extremely important and necessary.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of SERPINB10 Associated with Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps

Deng

She³

et al. 2022

Disease Markers

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Background. Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper airway inflammatory disorder with a high rate of postoperative recurrence. SERPINB10 is a proinflammatory cytokine expressed on epithelial cells, but its role in CRSwNP has not been described. This study is aimed at exploring the SERPINB10 expression in CRSwNP and its relationship with postoperative recidivation. Methods. We recruited 140 individuals, consisting of 60 patients with CRSwNP, 40 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 40 healthy controls (HCs). Tissue specimens were collected during the surgery, and SERPINB10 expression was determined by reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence. We determined the tissue SERPINB10 expression levels in CRSwNP and examined its clinical value in predicting postoperative recurrence. Results. We determined that tissue SERPINB10 mRNA and protein levels were increased in the CRSwNP group, especially in the recurrent CRSwNP group, compared with the CRSsNP and HC groups ( p < 0.05 ), and SERPINB10 mRNA levels were correlated with peripheral and tissue eosinophil counts and percentages ( p < 0.05 ). Binary logistic regression analysis and receiver operating characteristic (ROC) curves suggested that the expressions of tissue SERPINB10 mRNA were significantly linked to postoperative recurrence in CRSwNP patients ( AUC = 0.741 , p < 0.001 ). Conclusion. Elevated local SERPINB10 levels in patients with CRSwNP were related to tissue eosinophilic inflammation and disease recurrence. These data suggested that SERPINB10 might contribute to the eosinophilic inflammation in CRSwNP and appeared to be a potential biomarker for the prediction of relapse after surgery.

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Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis

Cited by 9 publications

References 66 publications

Ghrelin Downregulates Lipopolysaccharide/ Leptin-Induced MUC5AC Expression in Human Nasal Epithelial Cells

Ghrelin Downregulates Lipopolysaccharide/ Leptin-Induced MUC5AC Expression in Human Nasal Epithelial Cells

Evaluating the Association of Obesity and Chronic Rhinosinusitis: A Systematic Review and Meta‐analysis

Increased Expression of SERPINB10 Associated with Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps

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