식이유도 비만 마우스에서 칸나비디올(Cannabidiol) 오일의 체중 감량 효과에 대한 검증연구
Effect of Cannabidiol Oil on Weight Loss in Diet-Induced Obese Mice: Validation Study
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objectives This study aimed at investigating the pharmacological and physiological effects of cannabidiol (CBD) oil on weight loss in diet-induced obese (DIO) mice. Methods A DIO mice model was constructed with 33 C57BL/6 male mice, aged six weeks, who had been fed a high-fat diet for 13 weeks. Subsequently, 20 mg/kg (n=11) or 60 mg/kg (n=11) of CBD oil or sesame seed oil (n=11) per day was given along with a high-fat diet for four weeks. The body weight of each subject was measured weekly, and venous blood was drawn for biochemistry and enzyme-linked immunoassay before and after the four-week trial period. An oral glucose tolerance test was performed to assess glucose metabolism. At the end of the CBD oil treatment, dual-energy X-ray absorptiometry was used to calculate body fat composition, and the mesenteric adipose tissue was measured as representative of the fat mass of each subject. For statistical analysis, we used the Kruskal-Wallis test, Turkey’s test using ranks and generalized estimating equations. Results After administration of CBD oil (60 mg/kg) for four weeks, the DIO mice showed significant weight loss, compared to the sham control mice (p=0.027). Mice fed with 60 mg/kg of CBD oil also had a significant reduction in fat percentage (p=0.009) and mesenteric fat weight loss (p=0.024), compared to the sham control mice, even with higher food intake (p=0.029). Moreover, mice fed with 60 mg/kg of CBD oil showed a significant improvement in glucose tolerance (p=0.003) and lower plasma leptin levels (p=0.006). Conclusion This study shows that orally administered CBD oil induces weight loss in DIO mice. It has been postulated that CBD oil attenuates an over-activated endocannabinoid system, thereby increasing energy expenditure, and improving glucose metabolism and leptin resistance.
Abstract
Objectives This study aimed at investigating the pharmacological and physiological effects of cannabidiol (CBD) oil on weight loss in diet-induced obese (DIO) mice. Methods A DIO mice model was constructed with 33 C57BL/6 male mice, aged six weeks, who had been fed a high-fat diet for 13 weeks. Subsequently, 20 mg/kg (n=11) or 60 mg/kg (n=11) of CBD oil or sesame seed oil (n=11) per day was given along with a high-fat diet for four weeks. The body weight of each subject was measured weekly, and venous blood was drawn for biochemistry and enzyme-linked immunoassay before and after the four-week trial period. An oral glucose tolerance test was performed to assess glucose metabolism. At the end of the CBD oil treatment, dual-energy X-ray absorptiometry was used to calculate body fat composition, and the mesenteric adipose tissue was measured as representative of the fat mass of each subject. For statistical analysis, we used the Kruskal-Wallis test, Turkey’s test using ranks and generalized estimating equations. Results After administration of CBD oil (60 mg/kg) for four weeks, the DIO mice showed significant weight loss, compared to the sham control mice (p=0.027). Mice fed with 60 mg/kg of CBD oil also had a significant reduction in fat percentage (p=0.009) and mesenteric fat weight loss (p=0.024), compared to the sham control mice, even with higher food intake (p=0.029). Moreover, mice fed with 60 mg/kg of CBD oil showed a significant improvement in glucose tolerance (p=0.003) and lower plasma leptin levels (p=0.006). Conclusion This study shows that orally administered CBD oil induces weight loss in DIO mice. It has been postulated that CBD oil attenuates an over-activated endocannabinoid system, thereby increasing energy expenditure, and improving glucose metabolism and leptin resistance.
참고문헌 (38)
- Ritchie SA, "The link between abdominal obesity, metabolic syndrome and cardiovascular disease", Nutr Metab Cardiovasc Dis, 17, pp.319~326 (2007)
- Hruby A, "The epidemiology of obesity : a big picture", Pharmacoeconomics, 33, pp.673~689 (2015)
- Bielawiec P, "Phytocannabinoids:useful drugs for the treatment of obesity? Special focus on cannabidiol", Front Endocrinol (Lausanne), 11, pp.114~ (2020)
- Bermudez-Silva FJ, "The endocannabinoid system, eating behavior and energy homeostasis : the end or a new beginning?", Pharmacol Biochem Behav, 95, pp.375~382 (2010)
- Silvestro S, "Use of cannabidiol in the treatment of epilepsy : efficacy and security in clinical trials", Molecules, 24, pp.1459~ (2019)
- Ignatowska-Jankowska B, "Cannabidiol decreases body weight gain in rats : involvement of CB2 receptors", Neurosci Lett, 490, pp.82~84 (2011)
- Iuvone T, "Cannabidiol : a promising drug for neurodegenerative disorders?", CNS Neurosci Ther, 15, pp.65~75 (2009)
- Wierucka-Rybak M, "The effects of leptin in combination with a cannabinoid receptor 1 antagonist, AM 251, or cannabidiol on food intake and body weight in rats fed a high-fat or a free-choice high sugar diet", J Physiol Pharmacol, 65, pp.487~496 (2014)
- 장유진, "식이유도 비만 마우스에서 대마 추출물의 체중 감량 효과에 대한 예비 연구", 신경정신의학, 59(3), pp.260~267 (2020), 대한신경정신의학회[DOI]
- Pacini G, "Methods and models for metabolic assessment in mice", J Diabetes Res, 2013, pp.986906~ (2013)
- Russell WMS, "The principles of humane experimental technique" (1959), Methuen Publishing
- Chung Mo Koo, "Cannabidiol for Treating Lennox-Gastaut Syndrome and Dravet Syndrome in Korea", Journal of Korean Medical Science, 35(50), pp.1~9 (2020), 대한의학회[DOI]
- Stockings E, "Evidence for cannabis and cannabinoids for epilepsy : a systematic review of controlled and observational evidence", J Neurol Neurosurg Psychiatry, 89, pp.741~753 (2018)
- Prenderville JA, "The role of cannabinoids in adult neurogenesis", Br J Pharmacol, 172, pp.3950~3963 (2015)
- Malkesman O, "Animal models of suicide-trait-related behaviors", Trends Pharmacol Sci, 30, pp.165~173 (2009)
- Jadoon KA, "Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized: a randomized, double-blind, placebo-controlled, parallel group pilot study", Diabetes Care, 39, pp.1777~1786 (2016)
- Chusyd DE, "Relationships between rodent white adipose fat pads and human white adipose fat depots", Front Nutr, 3, pp.10~ (2016)
- Huestis MA, "Cannabidiol adverse effects and toxicity", Curr Neuropharmacol, 17, pp.974~989 (2019)
- Leehey MA, "Safety and tolerability of cannabidiol in Parkinson disease: an open label, doseescalation study", Cannabis Cannabinoid Res, 5, pp.326~336 (2020)
- Viudez-Martínez A, "Cannabidiol does not display drug abuse potential in mice behavior", Acta Pharmacol Sin, 40, pp.358~364 (2019)
- Korou LM, "Comparative antilipidemic effect of N-acetylcysteine and sesame oil administration in diet-induced hypercholesterolemic mice", Lipids Health Dis, 9, pp.23~ (2010)
- Williams LM, "The development of diet-induced obesity and glucose intolerance in C57BL", 6 mice on a high-fat diet consists of distinct phases, 2014, pp.9, e106159~
- Al-Goblan AS, "Mechanism linking diabetes mellitus and obesity", Diabetes Metab Syndr Obes, 7, pp.587~591 (2014)
- Schwartz MW, "Diabetes, obesity, and the brain", Science, 307, pp.375~379 (2005)
- Cluny NL, "Prevention of diet-induced obesity effects on body weight and gut microbiota in mice treated chronically with Δ9-tetrahydrocannabinol", PLoS One, 10, pp.e0144270~ (2015)
- Hildebrandt AL, "Antiobesity effects of chronic cannabinoid CB1 receptor antagonist treatment in diet-induced obese mice", Eur J Pharmacol, 462, pp.125~132 (2003)
- Friedman JM, "Leptin and the regulation of body weight in mammals", Nature, 395, pp.763~770 (1998)
- Shimomura I, "Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy", Nature, 401, pp.73~76 (1999)
- Morton GJ, "Leptin and the central nervous system control of glucose metabolism", Physiol Rev, 91, pp.389~411 (2011)
- Di Marzo V, "Leptin-regulated endocannabinoids are involved in maintaining food intake", Nature, 410, pp.822~825 (2001)
- Sarzani R, "Altered pattern of cannabinoid type 1 receptor expression in adipose tissue of dysmetabolic and overweight patients", Metabolism, 58, pp.361~367 (2009)
- Lu D, "Controlled downregulation of the cannabinoid CB1 receptor provides a promising approach for the treatment of obesity and obesity-derived type 2 diabetes", Cell Stress Chaperones, 21, pp.1~7 (2016)
- Blüher M, "Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity", Diabetes, 55, pp.3053~3060 (2006)
- Ravinet Trillou C, "Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice", Am J Physiol Regul Integr Comp Physiol, 284, pp.R345~R353 (2003)
- Wiley JL, "CB1 cannabinoid receptor-mediated modulation of food intake in mice", Br J Pharmacol, 145, pp.293~300 (2005)
- Gallily R, "Overcoming the bell-shaped doseresponse of cannabidiol by using cannabis extract enriched in cannabidiol", Pharmacol Pharm, 6, pp.75~85 (2015)
- Grotenhermen F, "Pharmacokinetics and pharmacodynamics of cannabinoids", Clin Pharmacokinet, 42, pp.327~360 (2003)
- Tam J, "Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by reversing leptin resistance", Cell Metab, 16, pp.167~179 (2012)