Lipoproteins carry endocannabinoids that inhibit the Hedgehog pathway

Khaliullina, Helena; Bilgin, Mesut; Sampaio, Júlio L.; Shevchenko, Andrej; Eaton, Suzanne

doi:10.1101/000570

Cited by 4 publications

(4 citation statements)

References 60 publications

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“…It is also unclear whether EC share a common mechanism of transport or multiple vehicles could be involved, depending on the EC class and physicochemical properties of their fatty acid moieties. Conceivably, in blood circulation EC might be associated with lipoproteins [16] that deliver lipids from the liver to peripheral tissues.…”

Section: Introductionmentioning

confidence: 99%

Quantitative profiling of endocannabinoids in lipoproteins by LC–MS/MS

et al. 2015

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Endocannabinoids belong to a diverse family of endogenous lipid bioregulators acting as physiological ligands of cannabinoid receptor type 1 and cannabinoid receptor type 2 in the central and peripheral nervous system. They are also present in nmol L(-1) concentrations in human blood plasma; however, their association with possible molecular carriers remains poorly characterized. Here we report on the quantification of 46 endogenous molecular species from five major classes of endocannabinoids and endocannabinoid-related compounds in three lipoprotein fractions of human blood plasma: VLDL, LDL, HDL, and in the plasma lipoprotein-free fraction. Although sizable quantities of endocannabinoid-related molecules are associated with lipoproteins, we identified the lipoprotein-free fraction as a major carrier of endocannabinoids in blood circulation with the exception of 2-acylglycerols, which are markedly abundant in VLDL.

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Section: Introductionmentioning

confidence: 99%

Quantitative profiling of endocannabinoids in lipoproteins by LC–MS/MS

et al. 2015

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“…Based on these observations, endocannabinoids function differently in the absence or presence of ethanol, suggesting that a potential interaction between endocannabinoids and ethanol is detrimental to development. Endocannabinoids have been shown to be conserved inhibitors of Hedgehog signaling (Khaliullina et al, 2015). A recent study has demonstrated that cannabinoids exacerbated alcohol teratogenesis through CB1 receptor-Hedgehog pathway in zebrafish (Fish et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Cannabinoids differentially modulate behavioral and developmental responses to ethanol in Drosophila

Tan

et al. 2021

Preprint

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Prolonged prenatal or adult exposure to ethanol is detrimental to mental and physical well-being, resulting in developmental abnormalities, progressive addiction and ultimate death. A growing number of studies have shown the therapeutic potential of cannabinoids in ethanol-related behaviors in mammals. However, the potential pharmacological actions of cannabinoids in ethanol responses have not been examined in the model organism Drosophila melanogaster. Here, we systematically investigated the effects of various cannabinoids on ethanol preference, ethanol sensitivity and tolerance, and ethanol-induced developmental defect in Drosophila. We showed that treatment with the phytocannabinoid cannabidiol (CBD) displayed a significant decrease in preference for consuming ethanol in adult flies. Interestingly, cannabinoids exhibited differential roles in short- and long- term ethanol tolerance in flies. Although cannabinoids had no detectable effects on short-term ethanol tolerance, CBD and the endocannabinoid anandamide (AEA) suppressed long-term tolerance to ethanol. Moreover, ethanol exposure delayed larval-to-pupal development and increased larval/pupal size. Unexpectedly, treatment with CBD or endocannabinoids did not attenuate ethanol-induced developmental delay, instead, exacerbated its detrimental effect. Thus, our systematical study reveals, for the first time, a differential role of the cannabinoids in the modulation of ethanol-related responses in Drosophila.

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“…Lastly, endogenous endocannabinoids, a family of compounds consisting of fatty acids and alcohols attached to various polar head moieties, are affiliated with lipoproteins with effects on signaling through SMO, or smoothened [27]. One action of SMO is to promote insulin-independent glucose uptake in skeletal muscle and brown adipose [28].…”

Section: Protein-lipid Networkmentioning

confidence: 99%

“…One action of SMO is to promote insulin-independent glucose uptake in skeletal muscle and brown adipose [28]. Importantly, the endocannabinoids do not appear to act through binding to known receptors such as PPARA and TRPV1 [27]. In addition, it has been found that targeted knock down of mouse Abhd6 (a 2-arachidonoylglycerol hydrolase important in brain endocannabinoid signaling) shielded mice from high-fat diet-induced obesity among other metabolic dysfunctions [29].…”

Section: Protein-lipid Networkmentioning

confidence: 99%

How Gene Networks Can Uncover Novel CVD Players

Parnell

Casas‐Agustench

Iyer

et al. 2014

Curr Cardiovasc Risk Rep

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Cardiovascular diseases (CVD) are complex, involving numerous biological entities from genes and small molecules to organ function. Placing these entities in networks where the functional relationships among the constituents are drawn can aid in our understanding of disease onset, progression and prevention. While networks, or interactomes, are often classified by a general term, say lipids or inflammation, it is a more encompassing class of network that is more informative in showing connections among the active entities and allowing better hypotheses of novel CVD players to be formulated. A range of networks will be presented whereby the potential to bring new objects into the CVD milieu will be exemplified.

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Lipoproteins carry endocannabinoids that inhibit the Hedgehog pathway

Cited by 4 publications

References 60 publications

Quantitative profiling of endocannabinoids in lipoproteins by LC–MS/MS

Quantitative profiling of endocannabinoids in lipoproteins by LC–MS/MS

Cannabinoids differentially modulate behavioral and developmental responses to ethanol in Drosophila

How Gene Networks Can Uncover Novel CVD Players

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