Leptin: From structural insights to the design of antagonists

Zabeau, Lennart; Peelman, Frank; Tavernier, Jan

doi:10.1016/j.lfs.2015.04.015

Cited by 19 publications

(5 citation statements)

References 146 publications

(202 reference statements)

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“…Leptin is a hormone mainly produced by adipocytes and acts as an efferent satiety signal by virtue of its action on the leptin receptor in the hypothalamus. 17 Zinc has been shown to affect serum leptin levels. Mantzoros et al 18 showed that leptin levels decrease in response to zinc depletion and increase with zinc supplementation.…”

Section: Introductionmentioning

confidence: 99%

Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls – a cross-sectional pilot study

Zepf

Rao

Runions

et al. 2017

NDT

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BackgroundResearch has implicated that changes in zinc (Zn) metabolism may be associated with the biological underpinnings of eating disorders, in particular anorexia nervosa. However, to date research on the role of Zn in patients with bulimia nervosa (BN) is scarce.ObjectiveWe aimed to explore serum Zn concentrations in young patients with BN, with a focus on the stage of the disorder, comparing acutely ill and recovered patients with BN with healthy controls.MethodsSerum Zn concentrations were obtained from healthy controls and from acutely ill and remitted young patients with BN. Mean duration of remission was 4.0±3.5 years.ResultsRemitted patients showed elevated serum Zn concentrations when compared to controls (Cohen’s d=2.022), but concentrations were still in the normal range. Acutely ill patients also had higher serum Zn levels when compared to controls (all values still being within the reference range, Cohen’s d=0.882). There was no difference between acutely ill and remitted patients with BN in serum Zn concentrations. Of note, remitted patients had a significantly higher body weight when compared to the other two groups. Overall, there were no significant differences in dietary preferences with regard to Zn containing foods between the groups.ConclusionThe present study provides preliminary evidence that the underlying factors for changes in Zn serum concentrations in young patients with BN do not vary with regard to the stage of illness (acute versus remitted BN). Further prospective research is needed in order to disentangle the possible interplay between serum Zn status and bulimic eating behaviors.

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Section: Introductionmentioning

confidence: 99%

Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls – a cross-sectional pilot study

Zepf

Rao

Runions

et al. 2017

NDT

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“…Thus, module network analysis together with functional analysis showed that (1) genes encoding signal transduction molecules constituted a substantial portion of genes in the compendium and (2) signaling molecules formed a dense network of physical and functional associations. According to the pathway analysis performed with DAVID, genes/proteins from overrepresented signaling pathways are involved in BW regulation, supporting the cellular response to well-known regulators of energy homeostasis, such as insulin [72], leptin [73], neurotrophins (BDNF, NGF) [74], adiponectin [75], PPARs [76], POMC [77], NPY [78], ghrelin [79], etc.…”

Section: Discussionmentioning

confidence: 99%

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

et al. 2016

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BackgroundObesity is heritable. It predisposes to many diseases. The objectives of this study were to create a compendium of genes relevant to feeding behavior (FB) and/or body weight (BW) regulation; to construct and to analyze networks formed by associations between genes/proteins; and to identify the most significant genes, biological processes/pathways, and tissues/organs involved in BW regulation.ResultsThe compendium of genes controlling FB or BW includes 578 human genes. Candidate genes were identified from various sources, including previously published original research and review articles, GWAS meta-analyses, and OMIM (Online Mendelian Inheritance in Man). All genes were ranked according to knowledge about their biological role in body weight regulation and classified according to expression patterns or functional characteristics. Substantial and overrepresented numbers of genes from the compendium encoded cell surface receptors, signaling molecules (hormones, neuropeptides, cytokines), transcription factors, signal transduction proteins, cilium and BBSome components, and lipid binding proteins or were present in the brain-specific list of tissue-enriched genes identified with TSEA tool. We identified 27 pathways from KEGG, REACTOME and BIOCARTA whose genes were overrepresented in the compendium. Networks formed by physical interactions or homological relationships between proteins or interactions between proteins involved in biochemical/signaling pathways were reconstructed and analyzed. Subnetworks and clusters identified by the MCODE tool included genes/proteins associated with cilium morphogenesis, signal transduction proteins (particularly, G protein–coupled receptors, kinases or proteins involved in response to insulin stimulus) and transcription regulation (particularly nuclear receptors). We ranked GWAS genes according to the number of neighbors in three networks and revealed 22 GWAS genes involved in the brain-specific PPI network. On the base of the most reliable PPIs functioning in the brain tissue, new regulatory schemes interpreting relevance to BW regulation are proposed for three GWAS genes (ETV5, LRP1B, and NDUFS3). ConclusionsA compendium comprising 578 human genes controlling FB or BW was designed, and the most significant functional groups of genes, biological processes/pathways, and tissues/organs involved in BW regulation were revealed. We ranked genes from the GWAS meta-analysis set according to the number and quality of associations in the networks and then according to their involvement in the brain-specific PPI network and proposed new regulatory schemes involving three GWAS genes (ETV5, LRP1B, and NDUFS3) in BW regulation. The compendium is expected to be useful for pathology risk estimation and for design of new pharmacological approaches in the treatment of human obesity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0466-2) contains supplementary material, which is available to authorized users.

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“…There are no leptin receptor antagonists currently available for clinical use. Lep locus III mutants are currently considered to have potential as antagonists (Zabeau et al, 2015). However, their precise location and nature remain controversial.…”

Section: Lep Analogue Lepr Antagonist and Ghrelinmentioning

confidence: 99%

LEP and LEPR are possibly a double‐edged sword for wound healing

Zhang¹,

Jia²,

et al. 2022

Journal Cellular Physiology

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Wound healing is a complex and error‐prone process. Wound healing in adults often leads to the formation of scars, a type of fibrotic tissue that lacks skin appendages. Hypertrophic scars and keloids can also form when the wound‐healing process goes wrong. Leptin (Lep) and leptin receptors (LepRs) have recently been shown to affect multiple stages of wound healing. This effect, however, is paradoxical for scarless wound healing. On the one hand, Lep exerts pro‐inflammatory and profibrotic effects; on the other hand, Lep can regulate hair follicle growth. This paper summarises the role of Lep and LepRs on cells in different stages of wound healing, briefly introduces the process of wound healing and Lep and LepRs, and examines the possibility of promoting scarless wound healing through spatiotemporal, systemic, and local regulation of Lep levels and the binding of Lep and LepRs.

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Leptin: From structural insights to the design of antagonists

Cited by 19 publications

References 146 publications

Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls – a cross-sectional pilot study

Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls – a cross-sectional pilot study

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

LEP and LEPR are possibly a double‐edged sword for wound healing

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Leptin: From structural insights to the design of antagonists

Cited by 19 publications

References 146 publications

Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls &ndash; a cross-sectional pilot study

Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls &ndash; a cross-sectional pilot study

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

LEP and LEPR are possibly a double‐edged sword for wound healing

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Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls – a cross-sectional pilot study

Differences in serum zinc levels in acutely ill and remitted adolescents and young adults with bulimia nervosa in comparison with healthy controls – a cross-sectional pilot study