Rimonabant improves metabolic parameters partially attributed to restoration of high voltage-activated Ca2+ channels in skeletal muscle in HFD-fed mice
Braz. j. med. biol. res
;
50(6): e6141, 2017. graf
Article
in English
| LILACS
| ID: biblio-839302
ABSTRACT
Cannabinoid type 1 receptor (CB1R) inhibition tends to be one of the promising strategies for the treatment of obesity and other related metabolic disorders. Although CB1R inhibition may cause adverse psychiatric effects including depression and anxiety, the investigation of the role of peripheral CB1R on weight loss and related metabolic parameters are urgently needed. We first explored the effect of rimonabant, a selective CB1R antagonist/inverse agonist, on some metabolic parameters in high fat-diet (HFD)-induced obesity in mice. Then, real-time PCR and electrophysiology were used to explore the contribution of high voltage-activated Ca2+ channels (HVACCs), especially Cav1.1, on rimonabant's effect in skeletal muscle (SM) in HFD-induced obesity. Five-week HFD feeding caused body weight gain, and decreased glucose/insulin tolerance in mice compared to those in the regular diet group (P<0.05), which was restored by rimonabant treatment compared to the HFD group (P<0.05). Interestingly, HVACCs and Cav1.1 were decreased in soleus muscle cells in the HFD group compared to the control group. Daily treatment with rimonabant for 5 weeks was shown to counter such decrease (P<0.05). Collectively, our findings provided a novel understanding for peripheral CB1R's role in the modulation of body weight and glucose homeostasis and highlight peripheral CB1R as well as Cav1.1 in the SM as potential targets for obesity treatment.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Piperidines
/
Pyrazoles
/
Blood Glucose
/
Calcium Channels
/
Muscle, Skeletal
/
Receptor, Cannabinoid, CB1
/
Cannabinoid Receptor Antagonists
Type of study:
Etiology study
/
Prognostic study
Limits:
Animals
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
2017
Type:
Article
Affiliation country:
China
Institution/Affiliation country:
Wuhan University/CN
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