Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis

Silvestri, Cristoforo; Paris, Debora; Martella, Andrea; Melck, Dominique; Guadagnino, Irene; Cawthorne, Mike A; Motta, Andréa; Marzo, Vincenzo Di

doi:10.1016/j.jhep.2015.01.001

Cited by 77 publications

(77 citation statements)

References 33 publications

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“…Likewise, a 5 μM dose of delta-9-tetrahydrocannabivarin (Δ 9 -THCV) increased yolk sac lipid mobilization at 48 h, and 72 h posttreatment. Although it remains to be seen whether these effects are due to peripheral or central actions, they are also consistent with the results of rodent studies where these compounds have been shown to decrease hepatic triglyceride levels (Silvestri et al, 2015, Wargent et al, 2013). …”

Section: Zebrafish Ecb Gene Functionsupporting

confidence: 76%

“…This notion is consistent with previous findings where the mutation of Cnr1 or the administration of SR141716A was shown to reduce food intake mice (Wiley et al, 2005). More recently, Silvestri et al examined the effects of systemic pCB administration on yolk sac metabolism in 3 dpf zebrafish (Silvestri et al, 2015). AdipoRed staining revealed that a 5 μM dose of cannabidiol (CBD) increased lipolysis at 24 h, 48 h, and 72 h posttreatment.…”

Section: Zebrafish Ecb Gene Functionmentioning

confidence: 99%

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Elucidating cannabinoid biology in zebrafish (Danio rerio)

Krug

Clark

2015

Gene

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The number of annual cannabinoid users exceeds 100,000,000 globally and an estimated 9 % of these individuals will suffer from dependency. Although exogenous cannabinoids, like those contained in marijuana, are known to exert their effects by disrupting the endocannabinoid system, a dearth of knowledge exists about the potential toxicological consequences on public health. Conversely, the endocannabinoid system represents a promising therapeutic target for a plethora of disorders because it functions to endogenously regulate a vast repertoire of physiological functions. Accordingly, the rapidly expanding field of cannabinoid biology has sought to leverage model organisms in order to provide both toxicological and therapeutic insights about altered endocannabinoid signaling. The primary goal of this manuscript is to review the existing field of cannabinoid research in the genetically tractable zebrafish model—focusing on the cannabinoid receptor genes, cnr1 and cnr2, and the genes that produce enzymes for synthesis and degradation of the cognate ligands anandamide and 2-arachidonylglycerol. Consideration is also given to research that has studied the effects of exposure to exogenous phytocannabinoids and synthetic cannabinoids that are known to interact with cannabinoid receptors. These results are considered in the context of either endocannabinoid gene expression or endocannabinoid gene function, and are integrated with findings from rodent studies. This provides the framework for a discussion of how zebrafish may be leveraged in the future to provide novel toxicological and therapeutic insights in the field of cannabinoid biology, which has become increasingly significant given recent trends in cannabis legislation.

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Section: Zebrafish Ecb Gene Functionsupporting

confidence: 76%

Section: Zebrafish Ecb Gene Functionmentioning

confidence: 99%

Elucidating cannabinoid biology in zebrafish (Danio rerio)

Krug

Clark

2015

Gene

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“…The cannabinoid THCV has been shown to produce weight loss and decreased body fat and serum leptin concentrations in obese mice (Riedel et al, 2009;Wargent et al, 2013). Additional support for this idea comes from recent work by Silvestri et al (2015) in which THCV and CBD were both shown to reduce accumulated lipid levels in adipocyctes and in a model of hepatosteatosis. Additional support for this idea comes from recent work by Silvestri et al (2015) in which THCV and CBD were both shown to reduce accumulated lipid levels in adipocyctes and in a model of hepatosteatosis.…”

Section: Obesitymentioning

confidence: 97%

Cannabis sativa and Hemp

Hartsel¹,

Eades²,

Hickory³

et al. 2016

Nutraceuticals

166

136

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“…All these effects were suggested to be due to non-CB1-mediated mechanisms. Additionally, like CBD, ⌬ 9 -THCV is very efficacious at inhibiting liver lipid accumulation in in vitro and in vivo models of steatosis, seemingly by stimulating lipolysis in hepatocytes via non-CB1, non-CB2-mediated mechanisms, and reduces lipid accumulation in white adipocytes (797). These results could have relevance on the future clinical development of ⌬ 9 -THCV for the treatment of hepatosteatosis and type 2 diabetes (556).…”

mentioning

confidence: 99%

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Ligresti¹,

Petrocellis²,

Marzo³

2016

Physiological Reviews

Self Cite

377

337

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Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one ⌬ 9 -tetrahydrocannabinol, and 2) the adaptive prohomeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

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Two non-psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis

Cited by 77 publications

References 33 publications

Elucidating cannabinoid biology in zebrafish (Danio rerio)

Elucidating cannabinoid biology in zebrafish (Danio rerio)

Cannabis sativa and Hemp

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

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