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

• Main Authors: Oosterveer Maaike H, Koolman Anniek H, de Boer Pieter T, Bos Trijnie, Bleeker Aycha, van Dijk Theo H, Bloks Vincent W, Kuipers Folkert, Sauer Pieter JJ, van Dijk Gertjan
• Format: Article
• Language: English
• Published: BMC 2011-12-01
• Series: Nutrition & Metabolism
• Subjects: CB₁-receptor; diet-induced adiposity; fat tissue; lipogenesis; lipolysis
• Online Access: http://www.nutritionandmetabolism.com/content/8/1/93

<p>Abstract</p> <p>Background</p> <p>Overactivity and/or dysregulation of the endocannabinoid system (ECS) contribute to development of obesity. <it>In vitro </it>studies indicate a regulatory role for the cannabinoid receptor 1 (CB₁) in adipocyte function and CB₁-receptor deficient (<it>CB₁^-/-</it>) mice are resistant to high fat diet-induced obesity. Whether this phenotype of <it>CB₁^-/-</it>mice is related to altered fat metabolism in adipose tissue is unknown.</p> <p>Methods</p> <p>We evaluated adipose tissue differentiation/proliferation markers and quantified lipogenic and lipolytic activities in fat tissues of <it>CB₁^-/-</it>and <it>CB₁^+/+</it>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 CB₁functioning.</p> <p>Results</p> <p>The adiposity-resistant phenotype of the <it>CB₁^-/-</it>mice was characterized by reduced fat mass and adipocyte size in HF and HF/FO-fed <it>CB₁^-/-</it>mice in parallel to a significant increase in energy expenditure as compared to <it>CB₁^+/+</it>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 <it>CB₁^-/-</it>and <it>CB₁^+/+</it>mice were unchanged. Whole-body and adipose-specific lipoprotein lipase (LPL) activities were also not altered in <it>CB₁^-/-</it>mice.</p> <p>Conclusions</p> <p>These findings indicate that protection against diet-induced adiposity in <it>CB₁</it>-deficient mice is not related to changes in adipocyte function <it>per se</it>, but rather results from increased energy dissipation by oxidative and non-oxidative pathways.</p>