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Leptin and Obesity: New Discoveries and Future Perspectives

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 20448

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Special Issue Editors

Dr. Marcos Carreira

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Guest Editor

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBEROBN), 28029 Madrid, Spain
Interests: leptin; adipose tissue; obesity treatment; food intake; brown adipose tissue; obesity induced diet; drug delivery
Special Issues, Collections and Topics in MDPI journals

Dr. Simona Frontoni

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Guest Editor

1. Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita, Fatebenefratelli Hospital, 00186 Rome, Italy
2. Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Interests: endocrinology; diabetology; obesity; hypertension; metabolic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Twenty-five years ago, leptin, a hormone produced and secreted by adipose tissue was discovered. From the first moment it was given a key role in the field of obesity, which also integrated different endocrine organs and physiological processes in the control of food intake and energy balance. However, the great therapeutic hopes of leptin in the treatment of obesity suddenly vanished, probably due to the lack of knowledge of the molecular mechanisms responsible for its effects. Even so, the research developed with leptin has made great contributions in the field of obesity. However, during the last few years very important advances have been evidenced in some of the mechanisms of action responsible for its effects on body weight control. All of this has meant a rejuvenated interest in this hormone that one day could lead to the much desired therapy against obesity.

In this Special Issue we welcome contributions related to any aspect of leptin and obesity. The idea is to provide readers with an idea of the mechanisms by which leptin exerts its effects on body weight regulation and its physiological relevance, mentioning the most recent and exciting discoveries.

Dr. Marcos Carreira
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
blood brain barrier
central nervous system
adipose tissue
leptin resistance
leptin transport
hypothalamus

Published Papers (6 papers)

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Research

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14 pages, 1951 KiB

Open AccessArticle

Leptin, Adiponectin, and Melatonin Modulate Colostrum Lymphocytes in Mothers with Obesity

by Gabrielle do Amaral Virginio Pereira, Tassiane Cristina Morais, Eduardo Luzia França, Blanca Elena Guerrero Daboin, Italla Maria Pinheiro Bezerra, Rafael Souza Pessoa, Ocilma Barros de Quental, Adenilda Cristina Honório-França and Luiz Carlos de Abreu

Int. J. Mol. Sci. 2023, 24(3), 2662; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032662 - 31 Jan 2023

Cited by 3 | Viewed by 1794

Abstract

Pregnancy complicated by obesity is associated with adverse triggered gestational and neonatal outcomes, with reductions in the subtypes of CD4+ T-lymphocytes representing the modulators of inflammation. It needs to be better established how maternal nutritional statuses impact the neuroendocrine–immune system’s action and affect the immunological mechanisms of the maternal–infant relationship via breastfeeding. This study examined the effects of maternal obesity on human colostrum lymphocytes and the intracellular mechanisms of lymphocyte modulation in the presence of leptin, adiponectin, and melatonin via cell proliferation; the release of intracellular calcium; and apoptosis induction. This cross-sectional study analyzed colostrum samples from 52 puerperal splits and divided them into overweight and eutrophic groups. Colostrum lymphocytes underwent immunophenotyping and cell proliferation by flow cytometry and intracellular calcium release and apoptosis assays by immunofluorescence in the presence or absence of hormones. Significant differences were considered when p < 0.05 by the chi-square or t-test. Maternal obesity reduced the population of T-lymphocytes and TCD4+ in human colostrum and proliferative activities (p < 0.05). These hormones restore lymphocyte proliferation to a level similar to the eutrophic group (p < 0.05). Leptin, adiponectin, melatonin hormones, and biological actions consolidated in the scientific literature also represent maternal and infant protection mechanisms via colostrum and the modulation of human colostrum lymphocytes. Full article

(This article belongs to the Special Issue Leptin and Obesity: New Discoveries and Future Perspectives)

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13 pages, 2630 KiB

Open AccessArticle

Gut Microbiota Restores Central Neuropeptide Deficits in Germ-Free Mice

by Sevag Hamamah and Mihai Covasa

Int. J. Mol. Sci. 2022, 23(19), 11756; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911756 - 04 Oct 2022

Cited by 13 | Viewed by 1712

Abstract

Recent work has demonstrated the ability of the gut microbiota (GM) to alter the expression and release of gut peptides that control appetite and regulate energy homeostasis. However, little is known about the neuronal response of these hormones in germ-free (GF) animals, especially leptin, which is strikingly low in these animals. Therefore, we aimed to determine the response to exogenous leptin in GF mice as compared to conventionally raised (CONV-R) mice. Specifically, we injected and measured serum leptin in both GF and CONV-R mice and measured expression of orexigenic and anorexigenic peptides NPY, AgRP, POMC, and CART in the hypothalamus and hindbrain to examine whether the GM has an impact on central nervous system regulation of energy homeostasis. We found that GF mice had a significant increase in hypothalamic NPY and AgRP mRNA expression and a decrease in hindbrain NPY and AgRP mRNA, while mRNA expression of POMC and CART remained unchanged. Administration of leptin normalized circulating levels of leptin, GLP-1, PYY, and ghrelin, all of which were significantly decreased in GF mice. Finally, brief conventionalization of GF mice for 10 days restored the deficits in hypothalamic and hindbrain neuropeptides present in GF animals. Taken together, these results show that the GM regulates hypothalamic and hindbrain orexigenic/anorexigenic neuropeptide expression. This is in line with the role of gut microbiota in lipid metabolism and fat deposition that may contribute to excess fat in conventionalized animals under high feeding condition. Full article

(This article belongs to the Special Issue Leptin and Obesity: New Discoveries and Future Perspectives)

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23 pages, 3099 KiB

Open AccessArticle

Leptin, Acting at Central Level, Increases FGF21 Expression in White Adipose Tissue via PPARβ/δ

by Lorena Mazuecos, Cristina Pintado, Blanca Rubio, Eduardo Guisantes-Batán, Antonio Andrés and Nilda Gallardo

Int. J. Mol. Sci. 2021, 22(9), 4624; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094624 - 28 Apr 2021

Cited by 9 | Viewed by 2725

Abstract

The altered function of adipose tissue can result in obesity, insulin resistance, and its metabolic complications. Leptin, acting on the central nervous system, modifies the composition and function of adipose tissue. To date, the molecular changes that occur in epididymal white adipose tissue (eWAT) during chronic leptin treatment are not fully understood. Herein we aimed to address whether PPARβ/δ could mediate the metabolic actions induced by leptin in eWAT. To this end, male 3-month-old Wistar rats, infused intracerebroventricularly (icv) with leptin (0.2 μg/day) for 7 days, were daily co-treated intraperitoneally (ip) without or with the specific PPARβ/δ receptor antagonist GSK0660 (1 mg/kg/day). In parallel, we also administered GSK0660 to control rats fed ad libitum without leptin infusion. Leptin, acting at central level, prevented the starvation-induced increase in circulating levels of FGF21, while induced markedly the endogenous expression of FGF21 and browning markers of eWAT. Interestingly, GSK0660 abolished the anorectic effects induced by icv leptin leading to increased visceral fat mass and reduced browning capacity. In addition, the pharmacological inhibition of PPARβ/δ alters the immunomodulatory actions of central leptin on eWAT. In summary, our results demonstrate that PPARβ/δ is involved in the up-regulation of FGF21 expression induced by leptin in visceral adipose tissue. Full article

(This article belongs to the Special Issue Leptin and Obesity: New Discoveries and Future Perspectives)

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16 pages, 2177 KiB

Open AccessArticle

Leptin Modulates the Response of Brown Adipose Tissue to Negative Energy Balance: Implication of the GH/IGF-I Axis

by Vicente Barrios, Laura M. Frago, Sandra Canelles, Santiago Guerra-Cantera, Eduardo Arilla-Ferreiro, Julie A. Chowen and Jesús Argente

Int. J. Mol. Sci. 2021, 22(6), 2827; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062827 - 11 Mar 2021

Cited by 11 | Viewed by 2631

Abstract

The growth hormone (GH)/insulin-like growth factor I (IGF-I) axis is involved in metabolic control. Malnutrition reduces IGF-I and modifies the thermogenic capacity of brown adipose tissue (BAT). Leptin has effects on the GH/IGF-I axis and the function of BAT, but its interaction with IGF-I and the mechanisms involved in the regulation of thermogenesis remains unknown. We studied the GH/IGF-I axis and activation of IGF-I-related signaling and metabolism related to BAT thermogenesis in chronic central leptin infused (L), pair-fed (PF), and control rats. Hypothalamic somatostatin mRNA levels were increased in PF and decreased in L, while pituitary GH mRNA was reduced in PF. Serum GH and IGF-I concentrations were decreased only in PF. In BAT, the association between suppressor of cytokine signaling 3 and the IGF-I receptor was reduced, and phosphorylation of the IGF-I receptor increased in the L group. Phosphorylation of Akt and cyclic AMP response element binding protein and glucose transporter 4 mRNA levels were increased in L and mRNA levels of uncoupling protein-1 (UCP-1) and enzymes involved in lipid anabolism reduced in PF. These results suggest that modifications in UCP-1 in BAT and changes in the GH/IGF-I axis induced by negative energy balance are dependent upon leptin levels. Full article

(This article belongs to the Special Issue Leptin and Obesity: New Discoveries and Future Perspectives)

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Review

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12 pages, 2268 KiB

Open AccessReview

Autonomic Nervous System in Obesity and Insulin-Resistance—The Complex Interplay between Leptin and Central Nervous System

by Benedetta Russo, Marika Menduni, Patrizia Borboni, Fabiana Picconi and Simona Frontoni

Int. J. Mol. Sci. 2021, 22(10), 5187; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105187 - 14 May 2021

Cited by 32 | Viewed by 6309

Abstract

The role of the autonomic nervous system in obesity and insulin-resistant conditions has been largely explored. However, the exact mechanisms involved in this relation have not been completely elucidated yet, since most of these mechanisms display a bi-directional effect. Insulin-resistance, for instance, can be caused by sympathetic activation, but, in turn, the associated hyperinsulinemia can activate the sympathetic branch of the autonomic nervous system. The picture is made even more complex by the implicated neural, hormonal and nutritional mechanisms. Among them, leptin plays a pivotal role, being involved not only in appetite regulation and glucose homeostasis but also in energy expenditure. The purpose of this review is to offer a comprehensive view of the complex interplay between leptin and the central nervous system, providing further insights on the impact of autonomic nervous system balance on adipose tissue and insulin-resistance. Furthermore, the link between the circadian clock and leptin and its effect on metabolism and energy balance will be evaluated. Full article

(This article belongs to the Special Issue Leptin and Obesity: New Discoveries and Future Perspectives)

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20 pages, 3424 KiB

Open AccessReview

Susceptibility and Severity of Viral Infections in Obesity: Lessons from Influenza to COVID-19. Does Leptin Play a Role?

by Valeria Guglielmi, Luca Colangeli, Monica D’Adamo and Paolo Sbraccia

Int. J. Mol. Sci. 2021, 22(6), 3183; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063183 - 20 Mar 2021

Cited by 22 | Viewed by 4371

Abstract

The recent pandemic Sars-CoV2 infection and studies on previous influenza epidemic have drawn attention to the association between the obesity and infectious diseases susceptibility and worse outcome. Metabolic complications, nutritional aspects, physical inactivity, and a chronic unbalance in the hormonal and adipocytokine microenvironment are major determinants in the severity of viral infections in obesity. By these pleiotropic mechanisms obesity impairs immune surveillance and the higher leptin concentrations produced by adipose tissue and that characterize obesity substantially contribute to such immune response dysregulation. Indeed, leptin not only controls energy balance and body weight, but also plays a regulatory role in the interplay between energy metabolism and immune system. Since leptin receptor is expressed throughout the immune system, leptin may exert effects on cells of both innate and adaptive immune system. Chronic inflammatory states due to metabolic (i.e., obesity) as well as infectious diseases increase leptin concentrations and consequently lead to leptin resistance further fueling inflammation. Multiple factors, including inflammation and ER stress, contribute to leptin resistance. Thus, if leptin is recognized as one of the adipokines responsible for the low grade inflammation found in obesity, on the other hand, impairments of leptin signaling due to leptin resistance appear to blunt the immunologic effects of leptin and possibly contribute to impaired vaccine-induced immune responses. However, many aspects concerning leptin interactions with inflammation and immune system as well as the therapeutical approaches to overcome leptin resistance and reduced vaccine effectiveness in obesity remain a challenge for future research. Full article

(This article belongs to the Special Issue Leptin and Obesity: New Discoveries and Future Perspectives)

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