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      Role of Leptin in the Digestive System

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          Abstract

          Leptin is a pluripotent peptide hormone produced mainly by adipocytes, as well as by other tissues such as the stomach. Leptin primarily acts on the central nervous system, particularly the hypothalamus, where this hormone regulates energy homeostasis and neuroendocrine function. Owing to this, disruption of leptin signaling has been linked with numerous pathological conditions. Recent studies have also highlighted the diverse roles of leptin in the digestive system including immune regulation, cell proliferation, tissue healing, and glucose metabolism. Of note, leptin acts differently under physiological and pathological conditions. Here, we review the current knowledge on the functions of leptin and its downstream signaling in the gastrointestinal tract and accessory digestive organs, with an emphasis on its physiological and pathological implications. We also discuss the current therapeutic uses of recombinant leptin, as well as its limitations.

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          Most cited references153

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          Mechanisms of hepatic stellate cell activation

          Activation of hepatic stellate cells (HSCs) in liver injury is the primary driver of hepatic fibrosis. In this Review, Tsuchida and Friedman detail the varied intracellular and extracellular signalling pathways leading to HSC activation, as well as the role of HSCs in liver fibrosis resolution and as therapeutic targets.
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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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              MAPK signal pathways in the regulation of cell proliferation in mammalian cells.

              MAPK families play an important role in complex cellular programs like proliferation, differentiation, development, transformation, and apoptosis. At least three MAPK families have been characterized: extracellular signal-regulated kinase (ERK), Jun kinase (JNK/SAPK) and p38 MAPK. The above effects are fulfilled by regulation of cell cycle engine and other cell proliferation related proteins. In this paper we discussed their functions and cooperation with other signal pathways in regulation of cell proliferation.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                12 April 2021
                2021
                : 12
                : 660040
                Affiliations
                [ 1 ]Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, United States
                [ 2 ]Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul, Korea
                Author notes

                Edited by: Thomas Brzozowski, Jagiellonian University Medical College, Poland

                Reviewed by: Oksana Zayachkivska, Danylo Halytsky Lviv National Medical University, Ukraine

                Jonathan Flak, Indiana Biosciences Research Institute, United States

                *Correspondence: Hyeyoung Kim, kim626@ 123456yonsei.ac.kr

                This article was submitted to Gastrointestinal and Hepatic Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                660040
                10.3389/fphar.2021.660040
                8086408
                33935782
                2c694f08-06c7-4fe9-b543-7dfb0bae1efc
                Copyright © 2021 Kim and Kim.

                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
                : 28 January 2021
                : 04 March 2021
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                leptin,digestive system,signal transduction,cytoprotection,immune system

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