Molecular determinants of the olfactory receptor Olfr544 activation by azelaic acid

Thach, Trung Thanh; Hong, Yu Jung; Lee, Sang-Ho; Lee, Sung Joon

doi:10.1016/j.bbrc.2017.02.104

Cited by 15 publications

(14 citation statements)

References 38 publications

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“…This notion is supported by a nonlinear dose-dependent effects of DEA (32) and a rapid onset and reversible activity at low micromolar doses of DEA in mammalian systems (unpublished data). Azelaic acid has a specific olfactory receptor, Olfr544, in mice (81). This receptor is expressed in several non-olfactory murine tissues, is highly abundant in muscle, and its activation by azelaic acid activates mitochondrial biogenesis (82).…”

Section: Discussionmentioning

confidence: 99%

Adaptive Membrane Fluidity Modulation: A Feedback Regulated Homeostatic System and Target for Pharmacological Intervention

Izbicka

Streeper

Louden³

2021

In Vivo

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Background/Aim: Alterations of plasma membrane fluidity are characteristic of many diseases but the intentional modulation of membrane fluidity with drugs has been less studied. We examined the therapeutic potential of the membrane fluidizer diethyl azelate (DEA) and related azelates. Materials and Methods: The effects of azelates on plasma membrane fluidity and cell signaling were examined in primary human and murine cells and in vivo. Endpoints were queried using single target and multiplexed immunoassays. Results: Unique membrane-fluidizing properties and biomarker signatures suggest that azelates are not prodrugs. DEA decreased cytokine signaling from pattern recognition receptors in human dendritic cells, disabled membrane attack of cholera toxin in vitro, and prevented immunosuppression by anthrax lethal toxin in vitro and in vivo. In the murine sepsis model, DEA increased survival and reduced organ damage. Conclusion: Azelates represent a new class of drugs, membrane active immunomodulators, which target an innate homeostatic mechanism, adaptive membrane fluidity modulation.

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Section: Discussionmentioning

confidence: 99%

Adaptive Membrane Fluidity Modulation: A Feedback Regulated Homeostatic System and Target for Pharmacological Intervention

Izbicka

Streeper

Louden³

2021

In Vivo

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“…Odorant receptors belong to the superfamily of G protein-coupled receptors (GPCRs) and are primarily expressed in the olfactory epithelium [55]. ORs are also found in several nonolfactory tissues, such as adipose, liver and intestine [56]. For example, activation of OR1A1 can suppress PPAR-γ expression in cultured hepatocytes and modulates hepatic triglyceride metabolism [57].…”

Section: Discussionmentioning

confidence: 99%

Microarray and metabolome analysis of hepatic response to fasting and subsequent refeeding in zebrafish (Danio rerio)

et al. 2019

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BackgroundCompensatory growth refers to the phenomenon in which organisms grow faster after the improvement of an adverse environment and is thought to be an adaptive evolution to cope with the alleviation of the hostile environment. Many fish have the capacity for compensatory growth, but the underlying cellular mechanisms remain unclear. In the present study, microarray and nontargeted metabolomics were performed to characterize the transcriptome and metabolome of zebrafish liver during compensatory growth.ResultsZebrafish could regain the weight they lost during 3 weeks of fasting and reach a final weight similar to that of fish fed ad libitum when refed for 15 days. When refeeding for 3 days, the liver displayed hyperplasia accompanied with decreased triglyceride contents and increased glycogen contents. The microarray results showed that when food was resupplied for 3 days, the liver TCA cycle (Tricarboxylic acid cycle) and oxidative phosphorylation processes were upregulated, while DNA replication and repair, as well as proteasome assembly were also activated. Integration of transcriptome and metabolome data highlighted transcriptionally driven alterations in metabolism during compensatory growth, such as altered glycolysis and lipid metabolism activities. The metabolome data also implied the participation of amino acid metabolism during compensatory growth in zebrafish liver.ConclusionOur study provides a global resource for metabolic adaptations and their transcriptional regulation during refeeding in zebrafish liver. This study represents a first step towards understanding of the impact of metabolism on compensatory growth and will potentially aid in understanding the molecular mechanism associated with compensatory growth.

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“…Olfr16 and its human homolog, OR10J5, can be activated by acetophenone, α-cedrene, and lyral ( von der Weid et al, 2015 ; Tong et al, 2017 ). Olfr544 is activated by azelaic acid ( Abaffy et al, 2007 ; Kang et al, 2015 ; Thach et al, 2017 ). Olfr57, Olfr99, and Olfr177, on the other hand, are all orphan receptors.…”

Section: Resultsmentioning

confidence: 99%

The Sensing Liver: Localization and Ligands for Hepatic Murine Olfactory and Taste Receptors

et al. 2020

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Sensory receptors, including olfactory receptors (ORs), taste receptors (TRs), and opsins (Opns) have recently been found in a variety of non-sensory tissues where they have distinct physiological functions. As G protein-coupled receptors (GPCRs), these proteins can serve as important chemosensors by sensing and interpreting chemical cues in the environment. We reasoned that the liver, the largest metabolic organ in the body, is primed to take advantage of some of these sensory receptors in order to sense and regulate blood content and metabolism. In this study, we report the expression of novel hepatic sensory receptors – including 7 ORs, 6 bitter TRs, and 1 Opn – identified through a systematic molecular biology screening approach. We further determined that several of these receptors are expressed within hepatocytes, the parenchymal cells of the liver. Finally, we uncovered several agonists of the previously orphaned hepatic ORs. These compounds fall under two classes: methylpyrazines and monoterpenes. In particular, the latter chemicals are plant and fungal-derived compounds with known hepatic protective effects. Collectively, this study sheds light on the chemosensory functions of the liver and unveils potentially important regulators of hepatic homeostasis.

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Molecular determinants of the olfactory receptor Olfr544 activation by azelaic acid

Cited by 15 publications

References 38 publications

Adaptive Membrane Fluidity Modulation: A Feedback Regulated Homeostatic System and Target for Pharmacological Intervention

Adaptive Membrane Fluidity Modulation: A Feedback Regulated Homeostatic System and Target for Pharmacological Intervention

Microarray and metabolome analysis of hepatic response to fasting and subsequent refeeding in zebrafish (Danio rerio)

The Sensing Liver: Localization and Ligands for Hepatic Murine Olfactory and Taste Receptors

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