GPR55 knockout mice had worse glucose tolerance, and the receptor partly mediated weight effects of rimonabant and THCV
Mice lacking the GPR55 receptor showed impaired glucose tolerance regardless of diet, and the weight-reducing effects of both rimonabant and THCV were partly mediated through GPR55.
Quick Facts
What This Study Found
GPR55 knockout mice had worse glucose tolerance than wildtype mice on both standard and high-fat diets, despite no differences in body weight, composition, food intake, or energy expenditure. Weight loss from rimonabant and THCV was reduced in knockout mice, suggesting GPR55 partially mediates their anti-obesity effects. Surprisingly, genotype did not affect these drugs' effects on glucose homeostasis.
Key Numbers
GPR55 knockouts had impaired glucose tolerance in both experiments. No genotype effect on body weight, composition, food intake, or energy expenditure. THCV (15 mg/kg) and rimonabant (10 mg/kg) produced less weight loss in knockouts. No genotype effect on drugs' glucose homeostasis effects.
How They Did This
GPR55 knockout and wildtype mice studied on standard chow and high-fat diets. Body weight, composition (DEXA and NMR), food intake, energy expenditure, locomotor activity, and glucose/insulin tolerance were measured. THCV (15 mg/kg) and rimonabant (10 mg/kg) were administered daily to both genotypes.
Why This Research Matters
GPR55 is an emerging cannabinoid receptor target. Understanding its role in metabolism could lead to new treatments for obesity and diabetes that work through the broader endocannabinoid system without the psychiatric side effects of CB1 blockers.
The Bigger Picture
After rimonabant was withdrawn due to psychiatric side effects, the search for metabolically active cannabinoid targets continued. GPR55 may offer a way to influence metabolism without the mood-related risks of CB1 antagonism.
What This Study Doesn't Tell Us
Knockout mice may have developmental compensatory mechanisms. Only male mice appear to have been studied. The disconnect between glucose tolerance and insulin tolerance findings is unexplained. Drug effects on glucose were not genotype-dependent despite effects on weight.
Questions This Raises
- ?Does GPR55 directly regulate insulin secretion?
- ?Could selective GPR55 agonists improve glucose tolerance without weight effects?
- ?Why did GPR55 genotype affect weight but not glucose responses to these drugs?
Trust & Context
- Key Stat:
- Impaired glucose tolerance in GPR55 knockouts without weight differences
- Evidence Grade:
- Well-designed preclinical study with multiple metabolic endpoints, but knockout model limitations and unexplained disconnect between weight and glucose findings.
- Study Age:
- 2020 animal study. Adds to understanding of GPR55's metabolic role and its interaction with cannabinoid drugs.
- Original Title:
- High fat-fed GPR55 null mice display impaired glucose tolerance without concomitant changes in energy balance or insulin sensitivity but are less responsive to the effects of the cannabinoids rimonabant or Δ(9)-tetrahydrocannabivarin on weight gain.
- Published In:
- PeerJ, 8, e9811 (2020)
- Authors:
- Wargent, Edward T, Kepczynska, Malgorzata, Zaibi, Mohamed Sghaier, Hislop, David C, Arch, Jonathan R S, Stocker, Claire J
- Database ID:
- RTHC-02907
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is THCV?
Tetrahydrocannabivarin (THCV) is a phytocannabinoid found in cannabis that has been studied for insulin-sensitizing and weight-reducing properties. Unlike THC, it does not produce strong psychoactive effects at typical doses.
Why was rimonabant withdrawn?
Rimonabant was a CB1 receptor blocker approved for weight loss in Europe but was withdrawn in 2008 due to serious psychiatric side effects including depression and suicidal thoughts. This study explores whether some of its metabolic effects work through GPR55 instead.
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Cite This Study
https://rethinkthc.com/research/RTHC-02907APA
Wargent, Edward T; Kepczynska, Malgorzata; Zaibi, Mohamed Sghaier; Hislop, David C; Arch, Jonathan R S; Stocker, Claire J. (2020). High fat-fed GPR55 null mice display impaired glucose tolerance without concomitant changes in energy balance or insulin sensitivity but are less responsive to the effects of the cannabinoids rimonabant or Δ(9)-tetrahydrocannabivarin on weight gain.. PeerJ, 8, e9811. https://doi.org/10.7717/peerj.9811
MLA
Wargent, Edward T, et al. "High fat-fed GPR55 null mice display impaired glucose tolerance without concomitant changes in energy balance or insulin sensitivity but are less responsive to the effects of the cannabinoids rimonabant or Δ(9)-tetrahydrocannabivarin on weight gain.." PeerJ, 2020. https://doi.org/10.7717/peerj.9811
RethinkTHC
RethinkTHC Research Database. "High fat-fed GPR55 null mice display impaired glucose tolera..." RTHC-02907. Retrieved from https://rethinkthc.com/research/wargent-2020-high-fatfed-gpr55-null
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.