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Novel Insights into the Physiological and Pathological Role of Leptin...
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Novel Insights into the Physiological and Pathological Role of Leptin and Leptin Receptor

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 15665

Special Issue Editors

Dr. Salvatore Panza

E-Mail Website
Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P. Bucci, 87036 Arcavacata di Rende, CS, Italy
Interests: breast cancer; glioblastoma; seminoma; obesity; leptin; aromatase
Special Issues, Collections and Topics in MDPI journals
Dr. Luca Gelsomino

E-Mail Website
Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy
Interests: breast cancer; tumor microenvironment; adipokines; nuclear receptors; ESR1 mutations; endocrine-resistance; exosomes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, research efforts have been expanded to clarify the role of leptin/leptin receptors in human physiology and in the pathophysiology of several disorders. However, more studies are needed to fully elucidate leptin/leptin receptor signaling pathways. The adipocyte-derived factor leptin and its receptor (ObR) are widely expressed in a large spectrum of tissues, wherein they play a pivotal role in energy homeostasis, metabolism, and in neuroendocrine and immune functions. Further, it has been demonstrated that the leptin/leptin receptor signaling pathway is linked to the proliferation, migration, and invasion of cancer cells. Indeed, targeting the leptin/leptin receptor has generated a great amount of interest in the design and development of several modulators that could offer a valuable therapeutic strategy in many diseases.

In this Special Issue, we welcome original research articles, as well as review articles, in order to provide new knowledge about the physiological and pathological significance of leptin/leptin receptors.

You may choose our Joint Special Issue in Receptors.

Dr. Salvatore Panza
Dr. Luca Gelsomino
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • leptin
  • leptin receptor
  • metabolic disorders
  • obesity
  • cancer

Published Papers (6 papers)

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Research

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13 pages, 1996 KiB  
Article
Clinical Significance of Plasma Leptin and Its Receptors mRNA Expression in Craniopharyngiomas: A Prospective Study
by Youchao Xiao, Wentao Wu, Kefan Cai, Lu Jin, Yanfei Jia, Ning Qiao, Fangzheng Liu, Siming Ru, Lei Cao and Songbai Gui
Biomolecules 2023, 13(7), 1078; https://doi.org/10.3390/biom13071078 - 05 Jul 2023
Viewed by 975
Abstract
Craniopharyngioma (CP) is a benign tumor with a high rate of obesity and frequent recurrence. Moreover, the role of leptin/leptin receptors axis in obesity and the prognosis of CP is still unknown. Plasma leptin concentration and mRNA expression of leptin receptors were assessed [...] Read more.
Craniopharyngioma (CP) is a benign tumor with a high rate of obesity and frequent recurrence. Moreover, the role of leptin/leptin receptors axis in obesity and the prognosis of CP is still unknown. Plasma leptin concentration and mRNA expression of leptin receptors were assessed in patients with CP. Moreover, the association between leptin/leptin receptors axis, weight-related outcomes, and progression-free survival (PFS) were explored in CP patients. Leptin receptors overexpressed in CP tumor tissue were compared to normal brain tissue (p < 0.05); compared to healthy controls, the concentration of leptin was elevated in CP with or without matched age, sex, and body mass index (BMI) (p < 0.05). The high plasma leptin level was an independent risk predictor for significant weight gain (adjusted odds ratio (aOR) = 2.29, and p = 0.030) and new-onset obesity (aOR = 6.64, and p = 0.016). High plasma leptin level (adjusted hazard ratio (aHR) = 3.74, and p = 0.011) and leptin receptor (LEPR) mRNA expression (aHR = 3.12, and p = 0.045) were independent risk factors for poor PFS in CP. Inappropriately elevated leptin relative to BMI and its failure to inhibit further weight gain indicate the existence of leptin resistance in patients with CP. Leptin and LEPR were independent predictors for PFS of patients with CP. The leptin/leptin receptors axis may be a potential therapeutic target for obesity in patients with CP. Full article
(This article belongs to the Special Issue Novel Insights into the Physiological and Pathological Role of Leptin and Leptin Receptor)
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19 pages, 1449 KiB  
Article
Leptin Receptor Deficiency Results in Hyperphagia and Increased Fatty Acid Mobilization during Fasting in Rainbow Trout (Oncorhynchus mykiss)
by Jamie L. Mankiewicz, Matthew J. Picklo, Joseph Idso and Beth M. Cleveland
Biomolecules 2022, 12(4), 516; https://doi.org/10.3390/biom12040516 - 29 Mar 2022
Cited by 5 | Viewed by 2421
Abstract
Leptin is a pleiotropic hormone known for regulating appetite and metabolism. To characterize the role of leptin signaling in rainbow trout, we used CRISPR/Cas9 genome editing to disrupt the leptin receptor (LepR) genes, lepra1 and lepra2. We compared wildtype (WT) and mutant [...] Read more.
Leptin is a pleiotropic hormone known for regulating appetite and metabolism. To characterize the role of leptin signaling in rainbow trout, we used CRISPR/Cas9 genome editing to disrupt the leptin receptor (LepR) genes, lepra1 and lepra2. We compared wildtype (WT) and mutant fish that were either fed to satiation or feed deprived for six weeks. The LepR mutants exhibited a hyperphagic phenotype, which led to heavier body weight, faster specific growth rate, increased viscero- and hepatosomatic indices, and greater condition factor. Muscle glycogen, plasma leptin, and leptin transcripts (lepa1) were also elevated in fed LepR mutant fish. Expression levels of several hypothalamic genes involved in feed regulation were analyzed (agrp, npy, orexin, cart-1, cart-2, pomc-a1, pomc-b). No differences were detected between fed WT and mutants except for pomc-b (proopiomelanocortin-b), where levels were 7.5-fold higher in LepR fed mutants, suggesting that pomc-b expression is regulated by leptin signaling. Fatty acid (FA) content did not statistically differ in muscle of fed mutant fish compared to WT. However, fasted mutants exhibited significantly lower muscle FA concentrations, suggesting that LepR mutants exhibit increased FA mobilization during fasting. These data demonstrate a key role for leptin signaling in lipid and energy mobilization in a teleost fish. Full article
(This article belongs to the Special Issue Novel Insights into the Physiological and Pathological Role of Leptin and Leptin Receptor)
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14 pages, 2105 KiB  
Article
Spexin Regulates Hypothalamic Leptin Action on Feeding Behavior
by Bora Jeong, Kwang-Kon Kim, Tae-Hwan Lee, Han-Rae Kim, Byong-Seo Park, Jeong-Woo Park, Jin-Kwon Jeong, Jae-Young Seong and Byung-Ju Lee
Biomolecules 2022, 12(2), 236; https://doi.org/10.3390/biom12020236 - 31 Jan 2022
Cited by 13 | Viewed by 3401
Abstract
Spexin (SPX) is a recently identified neuropeptide that is believed to play an important role in the regulation of energy homeostasis. Here, we describe a mediating function of SPX in hypothalamic leptin action. Intracerebroventricular (icv) SPX administration induced a decrease in food intake [...] Read more.
Spexin (SPX) is a recently identified neuropeptide that is believed to play an important role in the regulation of energy homeostasis. Here, we describe a mediating function of SPX in hypothalamic leptin action. Intracerebroventricular (icv) SPX administration induced a decrease in food intake and body weight gain. SPX was found to be expressed in cells expressing leptin receptor ObRb in the mouse hypothalamus. In line with this finding, icv leptin injection increased SPX mRNA in the ObRb-positive cells of the hypothalamus, which was blocked by treatment with a STAT3 inhibitor. Leptin also increased STAT3 binding to the SPX promoter, as measured by chromatin immunoprecipitation assays. In vivo blockade of hypothalamic SPX biosynthesis with an antisense oligodeoxynucleotide (AS ODN) resulted in a diminished leptin effect on food intake and body weight. AS ODN reversed leptin’s effect on the proopiomelanocortin (POMC) mRNA expression and, moreover, decreased leptin-induced STAT3 binding to the POMC promoter sequence. These results suggest that SPX is involved in leptin’s action on POMC gene expression in the hypothalamus and impacts the anorexigenic effects of leptin. Full article
(This article belongs to the Special Issue Novel Insights into the Physiological and Pathological Role of Leptin and Leptin Receptor)
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14 pages, 2047 KiB  
Article
Opposite Effects of Chronic Central Leptin Infusion on Activation of Insulin Signaling Pathways in Adipose Tissue and Liver Are Related to Changes in the Inflammatory Environment
by Vicente Barrios, Ana Campillo-Calatayud, Santiago Guerra-Cantera, Sandra Canelles, Álvaro Martín-Rivada, Laura M. Frago, Julie A. Chowen and Jesús Argente
Biomolecules 2021, 11(11), 1734; https://doi.org/10.3390/biom11111734 - 21 Nov 2021
Cited by 5 | Viewed by 1576
Abstract
Leptin modulates insulin signaling and this involves the Akt pathway, which is influenced by changes in the inflammatory environment and with leptin regulating cytokine synthesis. We evaluated the association between activation of the insulin-signaling pathway and alterations in pro- and anti-inflammatory cytokine levels [...] Read more.
Leptin modulates insulin signaling and this involves the Akt pathway, which is influenced by changes in the inflammatory environment and with leptin regulating cytokine synthesis. We evaluated the association between activation of the insulin-signaling pathway and alterations in pro- and anti-inflammatory cytokine levels in inguinal fat and liver of chronic central leptin infused (L), pair-fed (PF), and control rats. Signal transducer and activator of transcription 3 (STAT3) phosphorylation was increased in inguinal fat and reduced in liver of L rats. Phosphorylation of c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NFkB) was increased in inguinal fat of L rats, together with a pro-inflammatory cytokine profile, while in the liver activation of JNK and NFkB were reduced and an anti-inflammatory pattern was found. Phosphorylation of the insulin receptor, Akt and mechanistic target of rapamycin was decreased in inguinal fat and increased in liver of L rats. There was a direct relationship between pSTAT3 and JNK and a negative correlation of Akt with pSTAT3 and JNK in both tissues. These results indicate that the effects of chronically increased leptin on insulin-related signaling are tissue-specific and suggest that inflammation plays a relevant role in the crosstalk between leptin and insulin signaling. Full article
(This article belongs to the Special Issue Novel Insights into the Physiological and Pathological Role of Leptin and Leptin Receptor)
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Review

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30 pages, 2239 KiB  
Review
Leptin: A Heavyweight Player in Obesity-Related Cancers
by Amanda Caruso, Luca Gelsomino, Salvatore Panza, Felice Maria Accattatis, Giuseppina Daniela Naimo, Ines Barone, Cinzia Giordano, Stefania Catalano and Sebastiano Andò
Biomolecules 2023, 13(7), 1084; https://doi.org/10.3390/biom13071084 - 06 Jul 2023
Cited by 7 | Viewed by 3634
Abstract
Obesity, defined as the abnormal or excessive expansion of white adipose tissue, has reached pandemic proportions and is recognized as an important health concern since it is a common root for several comorbidities, including malignancies. Indeed, the current knowledge of the white adipose [...] Read more.
Obesity, defined as the abnormal or excessive expansion of white adipose tissue, has reached pandemic proportions and is recognized as an important health concern since it is a common root for several comorbidities, including malignancies. Indeed, the current knowledge of the white adipose tissue, which shifts its role from an energy storage tissue to an important endocrine and metabolic organ, has opened up new avenues for the discovery of obesity’s effects on tumor biology. In this review, we will report the epidemiological studies concerning the strong impact of obesity in several types of cancer and describe the mechanisms underlying the heterotypic signals between cancer cell lines and adipocytes, with particular emphasis on inflammation, the insulin/IGF-1 axis, and adipokines. Among the adipokines, we will further describe the in vitro, in vivo, and clinical data concerning the role of leptin, recognized as one of the most important mediators of obesity-associated cancers. In fact, leptin physiologically regulates energy metabolism, appetite, and reproduction, and several studies have also described the role of leptin in affecting cancer development and progression. Finally, we will summarize the newest pharmacological strategies aimed at mitigating the protumorigenic effects of leptin, underlining their mechanisms of action. Full article
(This article belongs to the Special Issue Novel Insights into the Physiological and Pathological Role of Leptin and Leptin Receptor)
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13 pages, 9537 KiB  
Review
Insight on the Role of Leptin: A Bridge from Obesity to Breast Cancer
by Roberto Buonaiuto, Fabiana Napolitano, Sara Parola, Pietro De Placido, Valeria Forestieri, Giovanna Pecoraro, Alberto Servetto, Luigi Formisano, Pietro Formisano, Mario Giuliano, Grazia Arpino, Sabino De Placido and Carmine De Angelis
Biomolecules 2022, 12(10), 1394; https://doi.org/10.3390/biom12101394 - 29 Sep 2022
Cited by 6 | Viewed by 2614
Abstract
Leptin is a peptide hormone, mainly known for its role as a mediator of adipose tissue endocrine functions, such as appetite control and energy homeostasis. In addition, leptin signaling is involved in several physiological processes as modulation of innate and adaptive immune responses [...] Read more.
Leptin is a peptide hormone, mainly known for its role as a mediator of adipose tissue endocrine functions, such as appetite control and energy homeostasis. In addition, leptin signaling is involved in several physiological processes as modulation of innate and adaptive immune responses and regulation of sex hormone levels. When adipose tissue expands, an imbalance of adipokines secretion may occur and increasing leptin levels contribute to promoting a chronic inflammatory state, which is largely acknowledged as a hallmark of cancer. Indeed, upon binding its receptor (LEPR), leptin activates several oncogenic pathways, such as JAK/STAT, MAPK, and PI3K/AKT, and seems to affect cancer immune response by inducing a proinflammatory immune polarization and eventually enhancing T-cell exhaustion. In particular, obesity-associated hyperleptinemia has been related to breast cancer risk development, although the underlying mechanism is yet to be completely clarified and needs to be deemed in light of multiple variables, such as menopausal state and immune response. The aim of this review is to provide an overview of the potential role of leptin as a bridge between obesity and breast cancer and to establish the physio-pathological basis of the linkage between these major health concerns in order to identify appropriate and novel therapeutic strategies to adopt in daily clinical practice. Full article
(This article belongs to the Special Issue Novel Insights into the Physiological and Pathological Role of Leptin and Leptin Receptor)
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