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

Van, Oosterveer, Koolman, De, Bos Trijnie, Bleeker Aycha, Bloks, Kuipers Folkert, Sauer

Description

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.

Sujets

• Adipose tissue
• Lipogénesis
• Lipolysis

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 7
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Oosterveer et al . Nutrition & Metabolism 2011, 8 :93 http://www.nutritionandmetabolism.com/content/8/1/93

R E S E A R C H Open Access Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function Maaike H Oosterveer 1* † , Anniek H Koolman 1,3 † , Pieter T de Boer 1 , Trijnie Bos 2 , Aycha Bleeker 1 , Theo H van Dijk 2 , Vincent W Bloks 1 , Folkert Kuipers 1,2 , Pieter JJ Sauer 1 and Gertjan van Dijk 3

Abstract 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. Keywords: CB 1 -receptor, diet-induced adiposity, fat tissue, lipogenesis, lipolysis

Background been identified. Because of its role in the central regulation The endocannabinoid system (ECS) comprises the endo-  of food intake and energy balance, the cannabinoid 1 genous cannabinoids (endocannabinoids or ECs), the can- (CB 1 )-receptor has emerged as an interesting drug target nabinoid receptors and the enzymes involved in the for treatment of obesity, dyslipidemia and insulin resis- synthesis and degradation of endocannabinoids [1]. The tance. CB 2 -receptors, on the other hand, are mainly two most studied ECs anandamide (AEA) and 2-arachido-  involved in immune function [3]. Administration of (endo) noyl glycerol (2-AG) are amides and esters, respectively, of cannabinoids increases food intake, while CB 1 -receptor long-chain polyunsaturated fatty acids (PUFAs) [2]. To antagonism results in hypophagia [4]. Mice deficient for date, two G protein-coupled cannabinoid receptors have the cannabinoid 1 receptor gene (Cnr1, further announced as CB 1-/- mice) are lean and have less fat stores compared * Correspondence: M [e-mail] to their wild type littermates [5]. This reduction in adipos- † Contributedequally . i i t n y g a t p h p a e t a C rs B t 1 o d b ef e ic i i n e d n e c p y e a n l d te e r n s t t o h f e f b o a o l d an in c ta b k e e t [ w 5 e ], en su e g n g e e r s g t y - 1 Department of Pediatrics, University Medical Center Groningen; University of e F Gr ul o l n l i is n t ge of n, a P u . t O h . or Bo in x f 3 r 0. m 0 a 0 t 1 io 9 n 7 i 0 s 0 a R v B aila Gr b o le ni a n t g t e h n e ,T e h n e d N of et t h h e e rla ar n ti d c s le intake, utilization and storage. o © 2011 Oosterveer et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.