The Leptin Receptor

Tartaglia, Louis A.

doi:10.1074/jbc.272.10.6093

Cited by 1,289Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesHypothalamic control of reproductive hormones

The Leptin Receptor

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Tartaglia, Louis A.·1997·Journal of Biological Chemistry

DOI 10.1074/jbc.272.10.6093

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Abstract

INTRODUCTIONOf the many genetic obesity syndromes, none have been as intensively studied as ob/ob and db/db mice. These two mutant mice were originally identified over 30 years ago (1Hummel K.P. Dickie M.M. Coleman D.L. Science. 1966; 153: 1127-1128Crossref PubMed Scopus (736) Google Scholar, 2Ingalls A.M. Dickie M.M. Snell G.D. J. Hered. 1950; 41: 317-318Crossref PubMed Scopus (642) Google Scholar) and shown to be a result of two distinct single gene mutations residing on mouse chromosomes 6 (ob) and 4 (db). The phenotypes and pathophysiologies of these two mice have been studied for decades and described in well over 1000 publications. However, the nature of the lesions or primary defects was not revealed until very recently.Perhaps the most informative early studies on the nature of the ob and db primary defects were the parabiosis experiments (partial connection of the circulatory systems of animals through grafting) performed throughout the 1970s (3Coleman D.L. Diabetologia. 1973; 9: 294-298Crossref PubMed Scopus (547) Google Scholar) (reviewed in Ref. 4Coleman D.L. Diabetologia. 1978; 14: 141-148Crossref PubMed Scopus (1074) Google Scholar). Parabiosis of an ob/ob mouse and a lean control resulted in partial normalization of body weight in the ob/ob mutant mouse. This led to the proposal that ob/ob mice were deficient in a circulating factor that could be restored through the blood of the lean animal. However, db/db mice that underwent parabiosis with lean controls did not exhibit body weight normalization. This suggested that db/db mice may be defective in their ability to respond to the putative satiety factor, perhaps because they were defective in the receptor for this molecule.The Obese (ob) Gene and Its Product, LeptinDespite intensive interest in the nature of the putative satiety factor missing in ob/ob mice, biochemical strategies failed to identify it. It was not until a genetic/positional cloning strategy was employed that the gene corresponding to the ob locus and its gene product were ultimately identified (5Zhang Y. Proenca R. Maffei M. Barone M. Leopold L. Friedman J.M. Nature. 1994; 372: 425-431Crossref PubMed Scopus (11625) Google Scholar). The wild type ob gene encodes a protein of about 16 kDa that is preceded by a secretory hydrophobic signal peptide. It is expressed in adipose tissue in multiple mammalian species including mice and humans. The development of antibody reagents confirmed that this factor (leptin) is found at high levels in blood, consistent with the previous parabiosis studies (6Maffei M. Halaas J. Ravussin E. Pratley R.E. Lee G.H. Zhang Y. Fei H. Kim S. Lallone R. Ranganathan S. Kern P.A. Freidman J.M. Nat. Med. 1995; 1: 1155-1161Crossref PubMed Scopus (3292) Google Scholar).Since the cloning of the ob gene numerous studies have described the regulation of the leptin mRNA and protein. Although the purpose of this review is not to comprehensively examine the growing literature on the regulation of the leptin ligand, it is important to briefly summarize a few aspects of leptin expression and regulation that are key in interpreting the biology of the leptin receptor. The leptin transcript appears to be expressed fairly specifically in adipose tissue (5Zhang Y. Proenca R. Maffei M. Barone M. Leopold L. Friedman J.M. Nature. 1994; 372: 425-431Crossref PubMed Scopus (11625) Google Scholar), although it is also detectable in human placenta on poly(A)- Northern blots. 1X. Weng and L. A. Tartaglia, unpublished observations. Steady state levels of the leptin mRNA and protein are elevated in a variety of rodent obesity models (6Maffei M. Halaas J. Ravussin E. Pratley R.E. Lee G.H. Zhang Y. Fei H. Kim S. Lallone R. Ranganathan S. Kern P.A. Freidman J.M. Nat. Med. 1995; 1: 1155-1161Crossref PubMed Scopus (3292) Google Scholar, 7Frederich R.C. Löllmann B. Hamann A. Napolitano-Rosen A. Kahn B.B. Lowell B.B. Flier J.S. J. 1995; PubMed Scopus Google Scholar, M. Halaas J. Ravussin E. Pratley R.E. Lee G.H. Zhang Y. Fei H. Kim S. Lallone R. Ranganathan S. Kern P.A. Freidman J.M. S. A. 1995; PubMed Scopus Google Scholar, H. S. A. PubMed Scopus Google Scholar). These have led to the proposal that leptin as an the body of the of in the adipose tissue that in and be the leptin receptor. regulation of the leptin transcript and protein also been in to in R.C. Löllmann B. Hamann A. Napolitano-Rosen A. Kahn B.B. Lowell B.B. Flier J.S. J. 1995; PubMed Scopus Google Scholar, H. S. A. PubMed Scopus Google Scholar, R. M. A. J. B. J. Nature. 1995; PubMed Scopus Google Scholar, R.C. Hamann A. S. B. Lowell B.B. Flier J.S. Nat. Med. 1995; 1: PubMed Scopus Google in and in It is that an important for leptin is the to Lowell B. E. Flier J.S. Nature. PubMed Scopus Google Scholar). on leptin mRNA and protein have also been in to a variety of including and R. M. A. J. B. J. Nature. 1995; PubMed Scopus Google Scholar, A. J. J. J. PubMed Scopus Google Scholar, J. A. A. Friedman J. J. PubMed Scopus Google al

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The leptin receptor contains an extracellular ligand-binding domain, a single transmembrane domain, and a cytoplasmic signaling domain, and is a member of the IL-6 receptor family of class 1 cytokine receptors.
“The leptin receptor contains an extracellular ligand-binding domain, a single transmembrane domain and a cytoplasmic signaling domain and is member of the interleukin (IL)-6 receptor family of class 1 cytokine receptors (182).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [182]

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Authors: Tartaglia, L. A.
Affiliations: Takeda Oncology (United States) (US)
Corresponding author: Tartaglia, Louis A.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1997-03
Volume: 272
Issue: 10
Pages: 6093-6096
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.272.10.6093
OpenAlex: W2014163208
Cited by: 1,289
References: 58
Citations by year: 2026: 5 · 2025: 8 · 2024: 9 · 2023: 17 · 2022: 25 · 2021: 24 · 2020: 15 · 2019: 18 · 2018: 17 · 2017: 35 · 2016: 38 · 2015: 38 · 2014: 62 · 2013: 65 · 2012: 64
FWCI: 6.39
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 8624 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords: leptin receptor, leptin, ob/ob mice, db/db mice, satiety factor, parabiosis, leptin signaling, leptin resistance, leptin receptor mutation, leptin receptor isoforms
MeSH terms: Animals, Body Weight, Carrier Proteins, Cloning, Molecular, Forecasting, Homeostasis, Humans, Obesity, Proteins, Receptors, Cell Surface, Signal Transduction, Receptors, Cytokine, Leptin, Mice, Rats, Receptors, Leptin

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