Identification of the nasal mucosa as a new target for leptin action

Taildeman, Jasmien; Demetter, Pieter; Rottiers, Isabelle; Holtappels, Gabriële; Bachert, Claus; Cuvelier, C; Pérez-Novo, Claudina

doi:10.1111/j.1365-2559.2010.03552.x

Cited by 5 publications

(7 citation statements)

References 44 publications

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“…Similar to the native protein, the LepNP85 conjugate at least in part used a saturable pathway for the distribution to the serum that was inhibited by co-administration of the free hormone. It is known that leptin receptors are expressed in human nasal mucosa [67–70] and serum levels of leptin were shown to positively correlate with that of nasal leptin in human [67]. Based on this, we believe that both the membrane binding of the PPO block and the receptor/transporter binding of the leptin might be responsible for the serum penetration of this conjugate after intranasal delivery.…”

Section: Discussionmentioning

confidence: 62%

Intranasal delivery of N-terminal modified leptin-pluronic conjugate for treatment of obesity

Yuan

Xiang

Zhao

et al. 2017

Journal of Controlled Release

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Leptin is an adipocyte-secreted hormone that is delivered via a specific transport system across the blood-brain barrier (BBB) to the brain where it acts on the hypothalamus receptors to control appetite and thermogenesis. Peripheral resistance to leptin due to its impaired brain delivery prevents therapeutic use of leptin in overweight and moderately obese patients. To address this problem, we modified the N-terminal amine of leptin with Pluronic P85 (LepNP85) and administered this conjugate intranasally using the nose-to-brain (INB) route to bypass the BBB. We compared this conjugate with the native leptin, the N-terminal leptin conjugate with poly(ethylene glycol) (LepNPEG5K), and two conjugates of leptin with Pluronic P85 attached randomly to the lysine amino groups of the hormone. Compared to the random conjugates of leptin with P85, LepNP85 has shown higher affinity upon binding with the leptin receptor, and similarly to native hormone activated hypothalamus receptors after direct injection into brain. After INB delivery, LepNP85 conjugate was transported to the brain and accumulated in the hypothalamus and hippocampus to a greater extent than the native leptin and LepNPEG5K and activated leptin receptors in hypothalamus at lower dose than native leptin. Our work suggests that LepNP85 can access the brain directly after INB delivery and confirms our hypothesis that the improvement in brain accumulation of this conjugate is due to its enhanced brain absorption. In conclusion, the LepNP85 with optimized conjugation chemistry is a promising candidate for treatment of obesity.

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Section: Discussionmentioning

confidence: 62%

Intranasal delivery of N-terminal modified leptin-pluronic conjugate for treatment of obesity

Yuan

Xiang

Zhao

et al. 2017

Journal of Controlled Release

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“…The Meta‐analysis of mean serum leptin levels of patients with CRS compared to healthy controls was completed on 2 eligible articles (Table 1). 10,11 Additionally, a separate Meta‐analysis was performed on 4 eligible studies that reported ORs on the prevalence of CRS based on the presence of overweight/obesity.…”

Section: Resultsmentioning

confidence: 99%

“…A recent systematic review on this topic found that the majority of the fifteen studies assessing the mean serum leptin levels of asthma patients with obesity reported elevated levels compared to the control subjects 9 . Similarly, previous research has found that patients with nasal polyposis have higher levels of serum leptin compared to healthy control subjects 10,11 …”

mentioning

confidence: 97%

“…9 Similarly, previous research has found that patients with nasal polyposis have higher levels of serum leptin compared to healthy control subjects. 10,11 Although obesity is a well-characterized risk factor for airway inflammatory diseases, specifically asthma, which has overlapping inflammation with CRS, its coprevalence and role in CRS is controversial. The prevalence of CRSsNP has been found to not be significantly higher in patients diagnosed with an overweight BMI (BMI ≥ 25 kg/m 2 ) compared to nonoverweight patients in 2 Korean cross-sectional studies.…”

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confidence: 99%

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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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“…In the nasal tract, upon injury, undifferentiated basal cells migrate from adjacent epithelium, spread over the denuded basement membrane, and proliferate in injured regions [7]. Despite leptin playing different roles in the olfactory mucosa cells [8], in the human nasal epithelium, its role is still largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor pathway in nasal cells

et al. 2014

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Leptin is involved in the lung epithelial homeostasis. Its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure leading to consequential structural abnormalities in the nasal epithelium. Topical corticosteroids are recommended as first-line therapy in AR. Parietaria pollen is one of the most important allergenic sources in the southern Europe. In vitro, in human nasal epithelial cell line RPMI 2650, we aimed to determine whether allergen stimulation acts on leptin/leptin receptor pathway and how fluticasone furoate (FF) influences this pathway. The effects of the major allergen recombinant Par j 1 (rPar j 1), of FF, of leptin, and of TGF-β1 on cell proliferation, on leptin/leptin receptor expression and modulation (by clonogenic test, by RT-q-RT-PCR, by immunocytochemistry and by flow-cytometry), and on STAT-3 activation (assessing nuclear translocation by western blot analysis) were assessed. We found that rPar j 1 and TGF-β1 significantly decreased cell proliferation and down-regulated the leptin/leptin receptor pathway, whereas FF and leptin reverted them, both alone and in combination. Furthermore, rPar j 1 reduced, while leptin and FF increased STAT-3 activation. In conclusion, FF and leptin itself are able to preserve nasal epithelial homeostasis restoring the leptin/leptin receptor pathway altered by rPar j 1 exposure.

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Identification of the nasal mucosa as a new target for leptin action

Abstract: Leptin receptors and their biological ligand leptin are expressed in the nasal mucosa, suggesting a possible role in upper airway immunology.

Cited by 5 publications

References 44 publications

Intranasal delivery of N-terminal modified leptin-pluronic conjugate for treatment of obesity

Intranasal delivery of N-terminal modified leptin-pluronic conjugate for treatment of obesity

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

Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor pathway in nasal cells

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