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大麻二酚通过影响脂肪酸转运蛋白的表达和抑制从头合成脂质来改善肌肉脂质谱。

Cannabidiol improves muscular lipid profile by affecting the expression of fatty acid transporters and inhibiting de novo lipogenesis.

机构信息

Department of Physiology, Medical University of Bialystok, Bialystok, Poland.

Department of Human Anatomy, Medical University of Bialystok, Bialystok, Poland.

出版信息

Sci Rep. 2023 Mar 6;13(1):3694. doi: 10.1038/s41598-023-30872-w.

DOI:10.1038/s41598-023-30872-w
PMID:36879113
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9988888/
Abstract

Obesity is one of the principal public health concerns leading to disturbances in glucose and lipid metabolism, which is a risk factor for several chronic diseases, including insulin resistance, type 2 diabetes mellitus, and cardiovascular diseases. In recent years, it turned out that cannabidiol (CBD) is a potential therapeutic agent in the treatment of obesity and its complications. Therefore, in the present study, we used CBD therapy (intraperitoneal injections in a dose of 10 mg/kg of body mass for 14 days) in a rat model of obesity induced by a high-fat diet (HFD). Gas-liquid chromatography and Western blotting were applied in order to determine the intramuscular lipid content and total expression of selected proteins in the white and red gastrocnemius muscle, respectively. Based on fatty acid composition, we calculated de novo lipogenesis ratio (16:0/18:2n-6), desaturation ratio (18:1n-9/18:0), and elongation ratios (18:0/16:0, 20:0/18:0, 22:0/20:0 and 24:0/22:0), in the selected lipid fractions. Two-week CBD administration significantly reduced the intramuscular fatty acids (FAs) accumulation and inhibited de novo lipogenesis in different lipid pools (in the free fatty acid, diacylglycerol, and triacylglycerol fractions) in both muscle types, which coincided with a decrease in the expression of membrane fatty acid transporters (fatty acid translocase, membrane-associated fatty acid binding protein, and fatty acid transport proteins 1 and 4). Moreover, CBD application profoundly improved the elongation and desaturation ratios, which was in line with downregulated expression of enzymes from the family of elongases and desaturases regardless of the metabolism presented by the muscle type. To our knowledge, this study is the first that outlines the novel effects of CBD action on skeletal muscle with different types of metabolism (oxidative vs. glycolytic).

摘要

肥胖是导致葡萄糖和脂质代谢紊乱的主要公共卫生问题之一,也是几种慢性疾病的危险因素,包括胰岛素抵抗、2 型糖尿病和心血管疾病。近年来,大麻二酚(CBD)已被证明是治疗肥胖及其并发症的一种有潜力的治疗药物。因此,在本研究中,我们使用 CBD 治疗(腹腔注射剂量为 10mg/kg 体重,持续 14 天)在高脂肪饮食(HFD)诱导的肥胖大鼠模型中。气相色谱和 Western blot 用于分别确定白肌和红肌的肌肉内脂质含量和选定蛋白的总表达。根据脂肪酸组成,我们计算了从头合成的脂肪酸比例(16:0/18:2n-6)、饱和度比例(18:1n-9/18:0)和伸长率比例(18:0/16:0、20:0/18:0、22:0/20:0 和 24:0/22:0),在选定的脂质馏分中。两周的 CBD 给药显著减少了不同脂质池(游离脂肪酸、二酰基甘油和三酰基甘油馏分)中肌肉内的脂肪酸(FA)积累,并抑制了从头合成,这与膜脂肪酸转运蛋白(脂肪酸转运蛋白、膜相关脂肪酸结合蛋白和脂肪酸转运蛋白 1 和 4)的表达减少一致。此外,CBD 的应用显著改善了伸长和饱和度比例,这与延长酶和去饱和酶家族的表达下调一致,而与肌肉类型的代谢无关。据我们所知,这项研究首次概述了 CBD 作用对具有不同代谢类型(氧化型与糖酵解型)的骨骼肌的新作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/49ceb8f2be44/41598_2023_30872_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/a830485fa2bc/41598_2023_30872_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/85a82cef8523/41598_2023_30872_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/00f97fb734d7/41598_2023_30872_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/0fc9feedda19/41598_2023_30872_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/3bf751deb3e4/41598_2023_30872_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/49ceb8f2be44/41598_2023_30872_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/cb56b1d0f663/41598_2023_30872_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/b2d01e27e52b/41598_2023_30872_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/4c8243b2178d/41598_2023_30872_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/a830485fa2bc/41598_2023_30872_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/85a82cef8523/41598_2023_30872_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/00f97fb734d7/41598_2023_30872_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/0fc9feedda19/41598_2023_30872_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/3bf751deb3e4/41598_2023_30872_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/272f/9988888/49ceb8f2be44/41598_2023_30872_Fig9_HTML.jpg

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