| Title |
The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity
|
|---|---|
| Published in |
Nutrition & Diabetes, May 2013
|
| DOI | 10.1038/nutd.2013.9 |
| Pubmed ID | |
| Authors |
E T Wargent, M S Zaibi, C Silvestri, D C Hislop, C J Stocker, C G Stott, G W Guy, M Duncan, V Di Marzo, M A Cawthorne |
| Abstract |
Background:Cannabinoid type-1 (CB1) receptor inverse agonists improve type 2 diabetes and dyslipidaemia but were discontinued due to adverse psychiatric effects. Δ(9)-Tetrahydrocannabivarin (THCV) is a neutral CB1 antagonist producing hypophagia and body weight reduction in lean mice. We investigated its effects in dietary-induced (DIO) and genetically (ob/ob) obese mice.Methods:We performed two dose-ranging studies in DIO mice; study 1: 0.3, 1, 2.5, 5 and 12.5 mg kg(-1), oral twice daily for 30 days and study 2: 0.1, 0.5, 2.5 and 12.5 mg kg(-1), oral, once daily for 45 days. One pilot (study 3: 0.3 and 3 mg kg(-1), oral, once daily) and one full dose-ranging (study 4: 0.1, 0.5, 2.5 and 12.5 mg kg(-1), oral, once daily) studies in ob/ob mice for 30 days. The CB1 inverse agonist, AM251, oral, 10 mg kg(-1) once daily or 5 mg kg(-1) twice daily was used as the positive control. Cumulative food and water intake, body weight gain, energy expenditure, glucose and insulin levels (fasting or during oral glucose tolerance tests), plasma high-density lipoprotein and total cholesterol, and liver triglycerides were measured. HL-5 hepatocytes or C2C12 myotubes made insulin-resistant with chronic insulin or palmitic acid were treated with 0, 1, 3 and 10 μM THCV or AM251.Results:THCV did not significantly affect food intake or body weight gain in any of the studies, but produced an early and transient increase in energy expenditure. It dose-dependently reduced glucose intolerance in ob/ob mice and improved glucose tolerance and increased insulin sensitivity in DIO mice, without consistently affecting plasma lipids. THCV also restored insulin signalling in insulin-resistant hepatocytes and myotubes.Conclusions:THCV is a new potential treatment against obesity-associated glucose intolerance with pharmacology different from that of CB1 inverse agonists/antagonists. |
X Demographics
The data shown below were collected from the profiles of 30 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 5 | 17% |
| Canada | 2 | 7% |
| Netherlands | 1 | 3% |
| Papua New Guinea | 1 | 3% |
| Bosnia and Herzegovina | 1 | 3% |
| Georgia | 1 | 3% |
| Unknown | 19 | 63% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 26 | 87% |
| Scientists | 3 | 10% |
| Practitioners (doctors, other healthcare professionals) | 1 | 3% |
Mendeley readers
The data shown below were compiled from readership statistics for 182 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 1% |
| Unknown | 180 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 32 | 18% |
| Student > Bachelor | 24 | 13% |
| Student > Ph. D. Student | 21 | 12% |
| Student > Master | 18 | 10% |
| Other | 16 | 9% |
| Other | 22 | 12% |
| Unknown | 49 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 24 | 13% |
| Medicine and Dentistry | 21 | 12% |
| Agricultural and Biological Sciences | 21 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 17 | 9% |
| Chemistry | 12 | 7% |
| Other | 30 | 16% |
| Unknown | 57 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 133. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 October 2023.
All research outputs
#314,988
of 25,482,409 outputs
Outputs from Nutrition & Diabetes
#31
of 476 outputs
Outputs of similar age
#2,126
of 207,922 outputs
Outputs of similar age from Nutrition & Diabetes
#1
of 13 outputs
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