Journal article
Renal effects of chronic pharmacological manipulation of CB2 receptors in rats with diet-induced obesity
British Journal of Pharmacology, Vol.173(7), pp.1128-1142
2016
PMID: 25537025
Abstract
Background and PurposeIn diabetic nephropathy agonism of CB2 receptors reduces albuminuria and podocyte loss; however, the role of CB2 receptors in obesity-related nephropathy is unknown. The aim of this study was to determine the role of CB2 receptors in a model of diet-induced obesity (DIO) and characterize the hallmark signs of renal damage in response to agonism (AM1241) and antagonism (AM630) of CB2 receptors.
Experimental ApproachMale Sprague Dawley rats were fed a high-fat diet (HFD: 40% digestible energy from lipids) for 10 weeks. In another cohort, after 9 weeks on a HFD, rats were injected daily with either 3mgkg(-1) AM1241, 0.3mgkg(-1) AM630 or saline for 6 weeks.
Key ResultsTen weeks on a HFD significantly reduced renal expression of CB2 receptors and renal function. Treatment with AM1241 or AM630 did not reduce weight gain or food consumption in DIO. Despite this, AM1241 significantly reduced systolic BP, peri-renal adipose accumulation, plasma leptin, urinary protein, urinary albumin, urinary sodium excretion and the fibrotic markers TGF-1, collagen IV and VEGF in kidney lysate. Treatment with AM630 of DIO rats significantly reduced creatinine clearance and increased glomerular area and kidney weight (gross and standardized for body weight). Diastolic BP, glucose tolerance, insulin sensitivity, plasma creatinine, plasma TGF-1 and kidney expression of fibronectin and -smooth muscle actin were not altered by either AM1241 or AM630 in DIO.
ConclusionsThis study demonstrates that while agonism of CB2 receptors with AM1241 treatment for 6 weeks does not reduce weight gain in obese rats, it leads to improvements in obesity-related renal dysfunction.
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Details
- Title
- Renal effects of chronic pharmacological manipulation of CB2 receptors in rats with diet-induced obesity
- Authors
- K. A. Jenkin - Victoria UniversityL. O'Keefe - Victoria UniversityA. C. Simcocks - Victoria UniversityJ. F. Briffa - The University of MelbourneM. L. Mathai - Florey Institute of Neuroscience and Mental HealthA. J. McAinch - Victoria UniversityD. H. Hryciw (Corresponding Author) - The University of Melbourne
- Publication details
- British Journal of Pharmacology, Vol.173(7), pp.1128-1142
- Publisher
- John Wiley & Sons Ltd.
- Date published
- 2016
- DOI
- 10.1111/bph.13056
- ISSN
- 1476-5381; 0007-1188
- PMID
- 25537025
- Grant note
- This work was supported by the Allen Foundation (D. H. H., A. J. M.), and through the Australian Government's Collaborative Research Networks (C. R. N.) programme (A. J. M.). Scholarship funding by Australian Postgraduate Award (K. A. J., L. O.) and Australian Rotary Health (A. C. S.).
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991187228502621
- Output Type
- Journal article
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