1. Department of Outpatient, Rocket Force Characteristic Medical Center,Beijing 100088,China; 2. Medical Innovation Research Division, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China; 3. Department of Stomatology, Rocket Force Characteristic Medical Center,Beijing 100088,China;
Abstract：Objective To explore the therapeutic effect and signaling mechanisms of cannabidiol (CBD) intervention on hepatic steatosis in aged mice fed with a high fat diet.Methods Thirty aged male C57BL/6J mice were randomly divided into three groups: normal diet group (NC), high-fat diet group (HFD) and cannabidiol intervention group (CBD). After intervention for 12 weeks, the serum levels of glucose,triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined by automatic biochemical analyzer, serum insulin level was detected by ELISA kit, and free fatty acid (FFA) level was determined by colorimetric analysis kit. Intraperitoneal glucose tolerance tests (IPGTT) and insulin tolerance test (ITT) were used to examine the glucose disposal ability. Lipid deposition in liver was detected by oil red O staining. The mRNA expression levels of lipid metabolism-related genes were evaluated by qRT-PCR. Western blot was used to detect the protein levels of AMPK and ACC.Results Compared with NC mice, the levels of blood glucose, TC, TG, FFA, ALT and AST in HFD mice significantly increased, and liver lipid deposition also increased (P<0.05). However, CBD intervention reduced the levels of parameters related to glucolipid metabolism (P<0.05), improved the ability of glucose disposal ability, alleviated lipid deposition in liver, and improved mRNA expression levels of lipid metabolism-related genes (P<0.05). Meanwhile, CBD significantly increased the protein expression levels of p-AMPK and p-ACC (P<0.05).Conclusion CBD alleviates hepatic steatosis in aged mice fed with a high fat diet, and AMPK/ACC signaling pathway may be involved in this progress.
Luo P, Qin C, Zhu L, et al. Ubiquitin-specific peptidase 10 (usp10) inhibits hepatic steatosis, insulin resistance, and inflammation through Sirt6[J]. Hepatology, 2018,68(5):1786-1803.
[2]
Zhang J L, Du B B, Zhang D H, et al. OTUB1 alleviates NASH through inhibition of the TRAF6-ASK1 signaling pathways[J]. Hepatology, 2022,75(5):1218-1234.
[3]
Younossi Z M, Golabi P, de Avila L, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis[J]. J Hepatol, 2019,71(4):793-801.
[4]
Zhu B, Mei W, Jiao T, et al. Neuregulin 4 alleviates hepatic steatosis via activating AMPK/mTOR-mediated autophagy in aged mice fed a high fat diet[J]. Eur J Pharmacol, 2020,884:173350.
[5]
Stefan N, Hring H U, Cusi K. Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies[J]. Lancet Diabetes Endocrinol, 2019,7(4):313-324.
[6]
Cluny N L, Reimer R A, Sharkey K A. Cannabinoid signalling regulates inflammation and energy balance: the importance of the brain-gut axis[J]. Brain Behav Immun, 2012,26(5):691-698.
[7]
Romero-Zerbo S Y, García-Fernández M, Espinosa-Jiménez V, et al. The atypical cannabinoid abn-CBD reduces inflammation and protects liver, pancreas, and adipose tissue in a mouse model of prediabetes and non-alcoholic fatty liver disease[J]. Front Endocrinol (Lausanne), 2020,11:103.
[8]
Yang L, Rozenfeld R, Wu D, et al. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy[J]. Free Radic Biol Med, 2014,68:260-267.
Hashimoto E, Tokushige K, Ludwig J. Diagnosis and classification of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: current concepts and remaining challenges[J]. Hepatol Res, 2015,45(1):20-28.
Liu H, Chen Y, Wen Y, et al. Phloridzin Ameliorates Lipid Deposition in High-Fat-Diet-Fed Mice with Nonalcoholic Fatty Liver Disease via Inhibiting the mTORC1/SREBP-1c Pathway[J]. J Agric Food Chem, 2021,69(31):8671-8683.
[13]
Li L, Zhang X, Ren H, et al. miR-23a/b-3p promotes hepatic lipid accumulation by regulating Srebp-1c and Fas[J]. J Mol Endocrinol, 2021,68(1):35-49.
[14]
Smati S, Régnier M, Fougeray T, et al. Regulation of hepatokine gene expression in response to fasting and feeding: Influence of PPAR-α and insulin-dependent signalling in hepatocytes[J]. Diabetes Metab, 2020,46(2):129-136.
[15]
Lai C Q, Parnell L D, Smith C E, et al. Carbohydrate and fat intake associated with risk of metabolic diseases through epigenetics of CPT1A[J]. Am J Clin Nutr, 2020,112(5):1200-1211.
[16]
Chen X, Zhang C, Zhao M, et al. Melatonin alleviates lipopolysaccharide-induced hepatic SREBP-1c activation and lipid accumulation in mice[J]. J Pineal Res, 2011,51(4):416-425.
[17]
Ho C, Gao Y, Zheng D, et al. Alisol A attenuates high-fat-diet-induced obesity and metabolic disorders via the AMPK/ACC/SREBP-1c pathway[J]. J Cell Mol Med, 2019,23(8):5108-5118.
[18]
Li L, Feng J, Sun L, et al. Cannabidiol promotes osteogenic differentiation of bone marrow mesenchymal stem cells in the inflammatory microenvironment via the CB2-dependent p38 MAPK signaling pathway[J]. Int J Stem Cells, 2022.
2022, Vol. 33 
