Cannabis exposure associated with weight reduction and β-cell protection in an obese rat model

被引:36
作者
Levendal, R-A. [1 ]
Schumann, D. [2 ]
Donath, M. [2 ]
Frost, C. L. [1 ]
机构
[1] Nelson Mandela Metropolitan Univ, Dept Biochem & Microbiol, ZA-6031 Port Elizabeth, South Africa
[2] Univ Basel Hosp, Div Endocrinol Diabet & Metab, CH-4031 Basel, Switzerland
基金
新加坡国家研究基金会;
关键词
Cafeteria diet; Cannabis; THC; Obesity; Cannabinoias; C-MYC EXPRESSION; ENDOCANNABINOID SYSTEM; INSULIN-SECRETION; HIGH-FAT; RECEPTORS; INTERLEUKIN-6; PHARMACOLOGY; BINDING;
D O I
10.1016/j.phymed.2012.02.001
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
The aim of this study was to investigate the effect of an organic cannabis extract on beta-cell secretory function in an in vivo diet-induced obese rat model and determine the associated molecular changes within pancreatic tissue. Diet-induced obese Wistar rats and rats fed on standard pellets were subcutaneously injected with an organic cannabis extract or the vehicle over a 28-day period. The effect of diet and treatment was evaluated using the intraperitoneal glucose tolerance tests (IPGTTs) and qPCR analysis on rat pancreata harvested upon termination of the experiment. The cafeteria diet induced an average weight difference of 32 g and an overall increase in body weight in the experimental groups occurred at a significantly slower rate than the control groups, irrespective of diet. Area under the curve for glucose (AUC(g)) in the obese group was significantly lower compared to the lean group (p < 0.001), with cannabis treatment significantly reducing the AUC(g) in the lean group (p < 0.05), and remained unchanged in the obese group, relative to the obese control group. qPCR analysis showed that the cafeteria diet induced down-regulation of the following genes in the obese control group, relative to lean controls: UCP2, c-MYC and FLIP. Cannabis treatment in the obese group resulted in up-regulation of CB( GLUT2, UCP2 and PKB, relative to the obese control group, while c-MYC levels were down-regulated, relative to the lean control group. Treatment did not significantly change gene expression in the lean group. These results suggest that the cannabis extract protects pancreatic islets against the negative effects of obesity. (C) 2012 Elsevier GmbH. All rights reserved.
引用
收藏
页码:575 / 582
页数:8
相关论文
共 42 条
[31]   MOLECULAR CHARACTERIZATION OF A PERIPHERAL RECEPTOR FOR CANNABINOIDS [J].
MUNRO, S ;
THOMAS, KL ;
ABUSHAAR, M .
NATURE, 1993, 365 (6441) :61-65
[32]   The emerging role of the endocannabinoid system in endocrine regulation and energy balance [J].
Pagotto, U ;
Marsicano, G ;
Cota, D ;
Lutz, B ;
Pasquali, R .
ENDOCRINE REVIEWS, 2006, 27 (01) :73-100
[33]   Action of Myc in vivo -: proliferation and apoptosis [J].
Pelengaris, S ;
Rudolph, B ;
Littlewood, T .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2000, 10 (01) :100-105
[34]   A new mathematical model for relative quantification in real-time RT-PCR [J].
Pfaffl, MW .
NUCLEIC ACIDS RESEARCH, 2001, 29 (09) :E45
[35]   Persistent Oxidative Stress Due to Absence of Uncoupling Protein 2 Associated with Impaired Pancreatic β-Cell Function [J].
Pi, Jingbo ;
Bai, Yushi ;
Daniel, Kiefer W. ;
Liu, Dianxin ;
Lyght, Otis ;
Edelstein, Diane ;
Brownlee, Michael ;
Corkey, Barbara E. ;
Collins, Sheila .
ENDOCRINOLOGY, 2009, 150 (07) :3040-3048
[36]   Increasing uncoupling protein-2 in pancreatic beta cells does not alter glucose-induced insulin secretion but decreases production of reactive oxygen species [J].
Produit-Zengaffinen, N. ;
Davis-Lameloise, N. ;
Perreten, H. ;
Becard, D. ;
Gjinovci, A. ;
Keller, P. A. ;
Wollheim, C. B. ;
Herrera, P. ;
Muzzin, P. ;
Assimacopoulos-Jeannet, F. .
DIABETOLOGIA, 2007, 50 (01) :84-93
[37]   Cannabinol derivatives: Binding to cannabinoid receptors and inhibition of adenylylcyclase [J].
Rhee, MH ;
Vogel, Z ;
Barg, J ;
Bayewitch, M ;
Levy, R ;
Hanus, L ;
Breuer, A ;
Mechoulam, R .
JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (20) :3228-3233
[38]   Biphasic effects of anandamide [J].
Sulcova, E ;
Mechoulam, R ;
Fride, E .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1998, 59 (02) :347-352
[39]  
van Wyk B.-E., 2000, PEOPLES PLANTS GUIDE, P158
[40]   CB1 cannabinoid receptor expression is regulated by glucose and feeding in rat pancreatic islets [J].
Vilches-Flores, Alonso ;
Laura Delgado-Buenrostro, Norma ;
Navarrete-Vazquez, Gabriel ;
Villalobos-Molina, Rafael .
REGULATORY PEPTIDES, 2010, 163 (1-3) :81-87