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Chronic Cannabidiol Administration Attenuates Skeletal Muscle De Novo Ceramide Synthesis Pathway and Related Metabolic Effects in a Rat Model of High-Fat Diet-Induced Obesity

Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland
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Biomolecules 2020, 10(9), 1241; https://doi.org/10.3390/biom10091241
Received: 31 July 2020 / Revised: 19 August 2020 / Accepted: 25 August 2020 / Published: 26 August 2020
Numerous studies showed that sustained obesity results in accumulation of bioactive lipid derivatives in several tissues, including skeletal muscle, which further contributes to the development of metabolic disturbances and insulin resistance (IR). The latest data indicate that a potential factor regulating lipid and glucose metabolism is a phytocannabinoid—cannabidiol (CBD), a component of medical marijuana (Cannabis). Therefore, we aimed to investigate whether chronic CBD administration influences bioactive lipid content (e.g., ceramide (CER)), as well as glucose metabolism, in the red skeletal muscle (musculus gastrocnemius) with predominant oxidative metabolism. All experiments were conducted on an animal model of obesity, i.e., Wistar rats fed a high-fat diet (HFD) or standard rodent chow, and subsequently injected with CBD in a dose of 10 mg/kg or its solvent for two weeks. The sphingolipid content was assessed using high-performance liquid chromatography (HPLC), while, in order to determine insulin and glucose concentrations, immunoenzymatic and colorimetric methods were used. The protein expression from sphingolipid and insulin signaling pathways, as well as endocannabinoidome components, was evaluated by immunoblotting. Unexpectedly, our experimental model revealed that the significantly intensified intramuscular de novo CER synthesis pathway in the HFD group was attenuated by chronic CBD treatment. Additionally, due to CBD administration, the content of other sphingolipid derivatives, i.e., sphingosine-1-phosphate (S1P) was restored in the high-fat feeding state, which coincided with an improvement in skeletal muscle insulin signal transduction and glycogen recovery. View Full-Text
Keywords: cannabidiol; obesity; insulin resistance; ceramide; sphingolipids; glucose; insulin signaling cannabidiol; obesity; insulin resistance; ceramide; sphingolipids; glucose; insulin signaling
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    Doi: 10.5281/zenodo.3968509
    Description: Figure S1: Representative Western blots showing the ratio of total expression of phosphorylated and unphosphorylated proteins involved in insulin signaling pathway e.g., (A) phosphorylated insulin receptor substrate 1/insulin receptor substrate 1 (pIRS-1/IRS-1), (B) phosphorylated protein kinase B/protein kinase B (pAkt/Akt), (C) phosphorylated AS160 protein/AS160 protein (pAS160/AS160) and (D) phosphorylated glycogen synthase kinase 3/glycogen synthase kinase 3 (pGSK-3/GSK-3) in the red gastrocnemius muscle in control and HFD groups after chronic CBD treatment. The total expressions of the above proteins were presented as a percentage difference compared to the control group, which was set as 100%. The data are expressed as mean values ± SD, n = 6 in each group. ap < 0.05 significant difference: control group vs. examined group; bp < 0.05 significant difference: HFD vs. HFD+CBD.
MDPI and ACS Style

Bielawiec, P.; Harasim-Symbor, E.; Konstantynowicz-Nowicka, K.; Sztolsztener, K.; Chabowski, A. Chronic Cannabidiol Administration Attenuates Skeletal Muscle De Novo Ceramide Synthesis Pathway and Related Metabolic Effects in a Rat Model of High-Fat Diet-Induced Obesity. Biomolecules 2020, 10, 1241. https://doi.org/10.3390/biom10091241

AMA Style

Bielawiec P, Harasim-Symbor E, Konstantynowicz-Nowicka K, Sztolsztener K, Chabowski A. Chronic Cannabidiol Administration Attenuates Skeletal Muscle De Novo Ceramide Synthesis Pathway and Related Metabolic Effects in a Rat Model of High-Fat Diet-Induced Obesity. Biomolecules. 2020; 10(9):1241. https://doi.org/10.3390/biom10091241

Chicago/Turabian Style

Bielawiec, Patrycja; Harasim-Symbor, Ewa; Konstantynowicz-Nowicka, Karolina; Sztolsztener, Klaudia; Chabowski, Adrian. 2020. "Chronic Cannabidiol Administration Attenuates Skeletal Muscle De Novo Ceramide Synthesis Pathway and Related Metabolic Effects in a Rat Model of High-Fat Diet-Induced Obesity" Biomolecules 10, no. 9: 1241. https://doi.org/10.3390/biom10091241

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