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Chronic endocannabinoid receptor‐1 antagonism improves metabolic parameters beyond those associated with reduced caloric intake in obese Zucker rats
Author(s) -
Lindborg Katherine Ann,
Henriksen Erik J
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.783.8
Subject(s) - medicine , endocrinology , antagonism , insulin resistance , endocannabinoid system , insulin , antagonist , chemistry , receptor , biology
We determined the effects of chronic endocannabinoid receptor‐1 (CB1R) antagonism on whole‐body metabolic parameters and skeletal muscle glucose transport in insulin‐resistant obese Zucker rat. Animals were assigned to one of three groups: an ad lib‐fed, vehicle‐treated group; a group treated with CB1R antagonist SR141716 (10 mg/kg i.p. for 14 d); or a pair‐fed, vehicle‐treated group. Food intake decreased 50% initially in SR141716 ‐treated animals and remained significantly reduced (p < 0.05) until day 13. Body weight was significantly reduced (~6%) by day 5 in both SR171416 ‐treated and pair‐fed animals compared to ad lib‐fed controls. Fasting plasma free fatty acids were reduced in the SR141716 ‐treated group (0.98 ± 0.09 mM) compared to the pair‐fed (1.20 ± 0.08) and ad lib‐fed (1.68 ± 0.14) groups. Chronic CB1R antagonism improved whole‐body insulin sensitivity (assessed during an oral glucose tolerance test) in the SR141716 ‐treated group compared to ad lib‐fed controls, primarily due to decreased insulin secretion. Moreover, treatment with SR141716 improved in vitro insulin‐stimulated glucose transport in soleus muscle (490 ± 26 pmol/mg/20min) compared to the pair‐fed (438 ± 10) and ad lib‐fed (391 ± 19) controls. These results indicate that chronic CB1R antagonism in obese Zucker rats induces metabolic improvements in whole‐body and skeletal muscle insulin action independent of reduced caloric intake.