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      Leptin and Obesity: Role and Clinical Implication

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          Abstract

          The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis. Leptin is a product of the obese ( ob) gene and, following synthesis and secretion from fat cells in white adipose tissue, binds to and activates its cognate receptor, the leptin receptor (LEP-R). LEP-R distribution facilitates leptin’s pleiotropic effects, playing a crucial role in regulating body mass via a negative feedback mechanism between adipose tissue and the hypothalamus. Leptin resistance is characterized by reduced satiety, over-consumption of nutrients, and increased total body mass. Often this leads to obesity, which reduces the effectiveness of using exogenous leptin as a therapeutic agent. Thus, combining leptin therapies with leptin sensitizers may help overcome such resistance and, consequently, obesity. This review examines recent data obtained from human and animal studies related to leptin, its role in obesity, and its usefulness in obesity treatment.

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          Most cited references179

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          Obesity is associated with macrophage accumulation in adipose tissue

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            Positional cloning of the mouse obese gene and its human homologue.

            The mechanisms that balance food intake and energy expenditure determine who will be obese and who will be lean. One of the molecules that regulates energy balance in the mouse is the obese (ob) gene. Mutation of ob results in profound obesity and type II diabetes as part of a syndrome that resembles morbid obesity in humans. The ob gene product may function as part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot.
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              Identification and expression cloning of a leptin receptor, OB-R.

              The ob gene product, leptin, is an important circulating signal for the regulation of body weight. To identify high affinity leptin-binding sites, we generated a series of leptin-alkaline phosphatase (AP) fusion proteins as well as [125I]leptin. After a binding survey of cell lines and tissues, we identified leptin-binding sites in the mouse choroid plexus. A cDNA expression library was prepared from mouse choroid plexus and screened with a leptin-AP fusion protein to identify a leptin receptor (OB-R). OB-R is a single membrane-spanning receptor most related to the gp130 signal-transducing component of the IL-6 receptor, the G-CSF receptor, and the LIF receptor. OB-R mRNA is expressed not only in choroid plexus, but also in several other tissues, including hypothalamus. Genetic mapping of the gene encoding OB-R shows that it is within the 5.1 cM interval of mouse chromosome 4 that contains the db locus.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                18 May 2021
                2021
                : 12
                : 585887
                Affiliations
                [1] 1 Department of Radiobiology and Molecular Genetics, “VINČA” Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade , Belgrade, Serbia
                [2] 2 Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), Computational Bioscience Research Center, Computer (CBRC), King Abdullah University of Science and Technology (KAUST) , Thuwal, Saudi Arabia
                [3] 3 School of Medicine, University of St Andrews , St Andrews, United Kingdom
                [4] 4 Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST) , Thuwal, Saudi Arabia
                Author notes

                Edited by: Hendrik Lehnert, University of Salzburg, Austria

                Reviewed by: Valeria Guglielmi, University of Rome Tor Vergata, Italy; Riccardo Dore, University of Lübeck, Germany

                *Correspondence: Esma R. Isenovic, isenovic@ 123456yahoo.com

                This article was submitted to Obesity, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2021.585887
                8167040
                34084149
                f11bbd68-f5c1-49c9-9074-e23606ae425b
                Copyright © 2021 Obradovic, Sudar-Milovanovic, Soskic, Essack, Arya, Stewart, Gojobori and Isenovic

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 July 2020
                : 30 April 2021
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 179, Pages: 14, Words: 6942
                Funding
                Funded by: King Abdullah University of Science and Technology 10.13039/501100004052
                Funded by: King Abdullah University of Science and Technology 10.13039/501100004052
                Funded by: King Abdullah University of Science and Technology 10.13039/501100004052
                Funded by: Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja 10.13039/501100004564
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                leptin-based therapies,obesity,leptin resistance,leptin receptor,leptin
                Endocrinology & Diabetes
                leptin-based therapies, obesity, leptin resistance, leptin receptor, leptin

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