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 (CB1) in adipocyte function and CB1-receptor deficient (CB1-/-) mice are resistant to high fat diet-induced obesity. Whether this phenotype of CB1-/- 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 CB1-/- and CB1+/+ 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 CB1 functioning.


RESULTS
The adiposity-resistant phenotype of the CB1-/- mice was characterized by reduced fat mass and adipocyte size in HF and HF/FO-fed CB1-/- mice in parallel to a significant increase in energy expenditure as compared to CB1+/+ 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 CB1-/- and CB1+/+ mice were unchanged. Whole-body and adipose-specific lipoprotein lipase (LPL) activities were also not altered in CB1-/- mice.


CONCLUSIONS
These findings indicate that protection against diet-induced adiposity in CB1-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.
Department of Pediatrics, University Medical Center Groningen; University of Groningen, P.O. Box 30.001 9700 RB Groningen, The Netherlands.
Maaike H
MH
Oosterveer
Department of Pediatrics, University Medical Center Groningen; University of Groningen, P.O. Box 30.001 9700 RB Groningen, The Netherlands.|Center for Behavior and Neurosciences, Unit Neuroendocrinology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
Anniek H
AH
Koolman
Department of Pediatrics, University Medical Center Groningen; University of Groningen, P.O. Box 30.001 9700 RB Groningen, The Netherlands.
Pieter T
PT
de Boer
Department of Laboratory Medicine, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen; University of Groningen, P.O. Box 30.001 9700 RB Groningen, The Netherlands.
Trijnie
T
Bos
Department of Pediatrics, University Medical Center Groningen; University of Groningen, P.O. Box 30.001 9700 RB Groningen, The Netherlands.
Aycha
A
Bleeker
Department of Laboratory Medicine, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen; University of Groningen, P.O. Box 30.001 9700 RB Groningen, The Netherlands.
Theo H
TH
van Dijk
Department of Pediatrics, University Medical Center Groningen; University of Groningen, P.O. Box 30.001 9700 RB Groningen, The Netherlands.
Vincent W
VW
Bloks
Department of Pediatrics, University Medical Center Groningen; University of Groningen, P.O. Box 30.001 9700 RB Groningen, The Netherlands.|Department of Laboratory Medicine, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen; University of Groningen, P.O. Box 30.001 9700 RB Groningen, The Netherlands.
Folkert
F
Kuipers
Department of Pediatrics, University Medical Center Groningen; University of Groningen, P.O. Box 30.001 9700 RB Groningen, The Netherlands.
Pieter Jj
PJ
Sauer
Center for Behavior and Neurosciences, Unit Neuroendocrinology, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
Gertjan
G
van Dijk