ABSTRACT
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which often includes obesity, diabetes, and dyslipidemia. Several studies in mice and humans have implicated the involvement of the gut microbiome in NAFLD. While cannabis and its phytocannabinoids may potentially be beneficial for treating metabolic disorders such as NAFLD, their effects on liver diseases and gut microbiota profile have yet to be addressed. In this study, we evaluated the therapeutic effects of the two major cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), on NAFLD progression. METHODS: NAFLD was induced by feeding mice a high fat-cholesterol diet (HFCD) for 6 weeks. During this period, the individual cannabinoids, THC or CBD, were added to the experimental diets at a concentration of 2.5 or 2.39 mg/kg. Profile of lipids, liver enzymes, glucose tolerance, and gene expression related to carbohydrate lipids metabolism and liver inflammation was analyzed. The effect of THC or CBD on microbiota composition in the gut was evaluated. RESULTS: While not alleviating hepatic steatosis, THC or CBD treatment influenced a number of parameters in the HFCD mouse model. CBD increased food intake, improved glucose tolerance, reduced some of the inflammatory response including TNFa and iNOS, and partially mitigated the microbiome dysbiosis observed in the HFCD fed mice. THC produced a much weaker response, only slightly reducing inflammatory-related gene expression and microbiome dysbiosis. CONCLUSIONS: The results of this study indicate the potential therapeutic effects of individual phytocannabinoids are different from the effects of the cannabis plant possessing a mixture of compounds. While CBD may help ameliorate symptoms of NAFLD, THC alone may not be as effective. This disparity can putatively be explained based on changes in the gut microbiota.
ABSTRACT
BACKGROUND: Dietary oils differ in their fatty acid composition and the presence of additional microcomponents (antioxidants, etc.). These differences are thought to invoke different biochemical pathways, thus affecting fats and carbohydrates metabolism differently. Olive oil (OO) and soybean oil (SO) are common vegetable oils in the local cuisine. Peanuts oils of local varieties are viewed as potential sources of dietary vegetable oils, especially in the food industry. OBJECTIVE: We examined the effect of four different dietary vegetable oils on carbohydrate and lipid metabolism in mice. The selected oils were OO, high in oleic acid, extracted from cultivated high oleic acid peanut (C-PO), regular peanut oil (PO), and SO. DESIGN: In this study, 32 male C57BL/6J mice were randomly divided into four groups (n = 8 in each group) and were fed with four different diets enriched with 4% (w/w) dietary vegetable oils (OO, C-PO, PO, or SO). After 10 weeks, the mice were sacrificed. Western blot was used to examine proteins such as phospho-AMP-activated protein kinase (p-AMPK), ace-tyl-CoA carboxylase (ACC), cluster of differentiation 36 (CD36), and Sirtuin 1 (SIRT1), whereas real-time polymerase chain reaction (PCR) was used to examine the expression of sterol regulatory element-binding protein-1c (SREBP-1C), fatty acid synthase (FAS), glucose-6-phosphatase (G6Pase), and CD36 transcripts. RESULTS: In mice-fed SO, lipid accumulation was predominately in adipose tissue, accompanied a tendency decrease in insulin sensitivity. Mice-fed OO had lower plasma triglycerides (TG) and increased hepatic CD36 gene expression. The C-PO group presented lower messenger RNA (mRNA) levels in the liver for all examined genes: SREBP-1c, FAS, G6Pase, and CD36. There were no significant differences in weight gain, plasma cholesterol and high-density lipoprotein (HDL) cholesterol levels, hepatic ACC, SIRT1, AMPK, and CD36 protein levels or in liver function among the diets. DISCUSSION: It seems that as long as fat is consumed in moderation, oil types may play a lesser role in the metabolism of healthy individuals. CONCLUSION: This finding has the potential to increase flexibility in choosing oil types for consumption.
