Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function

BACKGROUND: Overactivity and/or dysregulation of the endocannabinoid system (ECS) contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB(1)) in adipocyte function and CB(1)-receptor deficient (CB(1)(-/-)) mice are resistant to high fat diet-induced obesity. Whether this phenotype of CB(1)(-/- )mice is related to altered fat metabolism in adipose tissue is unknown. METHODS: We evaluated adipose tissue differentiation/proliferation markers and quantified lipogenic and lipolytic activities in fat tissues of CB(1)(-/- )and CB(1)(+/+ )mice fed a high-fat (HF) or a high-fat/fish oil (HF/FO) diet as compared to animals receiving a low-fat chow diet. Comparison between HF diet and HF/FO diet allowed to investigate the influence of dietary fat quality on adipose tissue biology in relation to CB(1 )functioning. RESULTS: The adiposity-resistant phenotype of the CB(1)(-/- )mice was characterized by reduced fat mass and adipocyte size in HF and HF/FO-fed CB(1)(-/- )mice in parallel to a significant increase in energy expenditure as compared to CB(1)(+/+ )mice. The expression levels of adipocyte differentiation and proliferation markers were however maintained in these animals. Consistent with unaltered lipogenic gene expression, the fatty acid synthesis rates in adipose tissues from CB(1)(-/- )and CB(1)(+/+ )mice were unchanged. Whole-body and adipose-specific lipoprotein lipase (LPL) activities were also not altered in CB(1)(-/- )mice. CONCLUSIONS: These findings indicate that protection against diet-induced adiposity in CB(1)-deficient mice is not related to changes in adipocyte function per se, but rather results from increased energy dissipation by oxidative and non-oxidative pathways.