The soluble leptin receptor

Schaab, Michael; Kratzsch, Juergen

doi:10.1016/j.beem.2015.08.002

Cited by 90 publications

(68 citation statements)

References 74 publications

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“…Ob‐Rb receptor is the only isoform that has an elongated intracellular domain with the required sequences for signal transduction. This isoform has 3 conserved tyrosines in its intracellular domain that allow the binding of molecules responsible for the activation of different signaling pathways, being the only isoform capable of promoting the activation of the JAK STAT3 cellular signaling pathway . Several studies have demonstrated that one of the main forms of leptin activity occurs through the activation of the pathway JAK2‐STAT3, which has been pointed out as one of the main mechanisms by which leptin promotes satiety and control of energy expenditure …”

Section: Leptin Receptors and Signalingmentioning

confidence: 99%

“…This isoform has 3 conserved tyrosines in its intracellular domain that allow the binding of molecules responsible for the activation of different signaling pathways, being the only isoform capable of promoting the activation of the JAK STAT3 cellular signaling pathway. 43,47,49,50 Several studies have demonstrated that one of the main forms of leptin activity occurs through the activation of the pathway JAK2-STAT3, which has been pointed out as one of the main mechanisms by which leptin promotes satiety and control of energy expenditure. 27,35,36,51,52 In response to the association of leptin, the Ob-Rb receptor undergoes a process of dimerization and conformational change, which induces the catalytic activity of the protein JAK2, and thus, leading to the phosphorylation of 3 tyrosine residues located in the Ob-Rb receptor, which promotes the activation of different signaling proteins.…”

Section: Leptin Receptors and Signalingmentioning

confidence: 99%

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Leptin in the regulation of the immunometabolism of adipose tissue-macrophages

Monteiro

Pereira

Palhinha

et al. 2019

Journal of Leukocyte Biology

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Obesity is a pandemic disease affecting around 15% of the global population. Obesity is a major risk factor for other conditions, such as type 2 diabetes and cardiovascular diseases. The adipose tissue is the main secretor of leptin, an adipokine responsible for the regulation of food intake and energy expenditure. Obese individuals become hyperleptinemic due to increased adipogenesis. Leptin acts through the leptin receptor and induces several immunometabolic changes in different cell types, including adipocytes and Mϕs. Adipose tissue resident Mϕs (ATMs) are the largest leukocyte population in the adipose tissue and these ATMs are in constant contact with the excessive leptin levels secreted in obese conditions. Leptin activates both the JAK2‐STAT3 and the PI3K‐AKT‐mTOR pathways. The activation of these pathways leads to intracellular metabolic changes, with increased glucose uptake, upregulation of glycolytic enzymes, and disruption of mitochondrial function, as well as immunologic alterations, such as increased phagocytic activity and proinflammatory cytokines secretion. Here, we discuss the immunometabolic effects of leptin in Mϕs and how hyperleptinemia can contribute to the low‐grade systemic inflammation in obesity.

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Section: Leptin Receptors and Signalingmentioning

confidence: 99%

Section: Leptin Receptors and Signalingmentioning

confidence: 99%

Leptin in the regulation of the immunometabolism of adipose tissue-macrophages

Monteiro

Pereira

Palhinha

et al. 2019

Journal of Leukocyte Biology

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“…Transport of leptin across the blood–brain barrier is facilitated by leptin receptors with short intracellular domains [commonly referred to as the ObRa paralog, as opposed to the ObRb paralog, which has a complete intracellular domain and is capable of mediating intracellular signaling (99, 100)]. This transport can be inhibited by a soluble form of the leptin receptor (ObRe), capable of binding leptin in serum (101, reviewed in 102). Sequencing cDNAs indicates that these isoforms are the result of alternate splicing of LEPR [e.g., Ref.…”

Section: Evolution Of Leptin Signaling: What Does Gene Evolution Tellmentioning

confidence: 99%

“…Sequencing cDNAs indicates that these isoforms are the result of alternate splicing of LEPR [e.g., Ref. (103)]; however, soluble receptors can also result from cleaving of membrane bound leptin receptors (102). All studies on leptin resistance (to our knowledge) are conducted in mammal models.…”

Section: Evolution Of Leptin Signaling: What Does Gene Evolution Tellmentioning

confidence: 99%

On the Molecular Evolution of Leptin, Leptin Receptor, and Endospanin

et al. 2017

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Over a decade passed between Friedman’s discovery of the mammalian leptin gene (1) and its cloning in fish (2) and amphibians (3). Since 2005, the concept of gene synteny conservation (vs. gene sequence homology) was instrumental in identifying leptin genes in dozens of species, and we now have leptin genes from all major classes of vertebrates. This database of LEP (leptin), LEPR (leptin receptor), and LEPROT (endospanin) genes has allowed protein structure modeling, stoichiometry predictions, and even functional predictions of leptin function for most vertebrate classes. Here, we apply functional genomics to model hundreds of LEP, LEPR, and LEPROT proteins from both vertebrates and invertebrates. We identify conserved structural motifs in each of the three leptin signaling proteins and demonstrate Drosophila Dome protein’s conservation with vertebrate leptin receptors. We model endospanin structure for the first time and identify endospanin paralogs in invertebrate genomes. Finally, we argue that leptin is not an adipostat in fishes and discuss emerging knockout models in fishes.

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“…High leptin levels suppress hunger by interacting with the long form of the leptin receptor (OB-RL) in the hypothalamus 7 . The soluble form of leptin receptor (sOB-R), which is produced through ectodomain shedding of OB-RL in peripheral tissues, can bind leptin in circulation, and thereby reduce its effect on the central nervous system 8 . The LEPR locus has previously been implicated in monogenic morbid obesity 9,10 , severe childhood obesity 11 , age of menarche 12 , age of voice breaking 13 , levels of fibrinogen 14 and C-reactive protein 15 , several blood cell count traits 16,17 , and plasma sOB-R levels 17,18 .…”

mentioning

confidence: 99%