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Published VersionCC BY V4.0, Open
Journal article
Treatment of Diet-Induced Obese Rats with CB2 Agonist AM1241 or CB2 Antagonist AM630 Reduces Leptin and Alters Thermogenic mRNA in Adipose Tissue
International Journal of Molecular Sciences, Vol.24(8), pp.1-14
2023
PMID: 37108770
Abstract
Diet-induced obesity (DIO) is a contributor to co-morbidities, resulting in alterations in hormones, lipids, and low-grade inflammation, with the cannabinoid type 2 receptor (CB2) contributing to the inflammatory response. The effects of modulating CB2 with pharmacological treatments on inflammation and adaptations to the obese state are not known. Therefore, we aimed to investigate the molecular mechanisms in adipose tissue of CB2 agonism and CB2 antagonism treatment in a DIO model. Male Sprague Dawley rats were placed on a high-fat diet (HFD) (21% fat) for 9 weeks, then received daily intraperitoneal injections with a vehicle, AM630 (0.3 mg/kg), or AM1241 (3 mg/kg), for a further 6 weeks. AM630 or AM1241 treatment in DIO rats did not alter their body weight, food intake, or liver weight, and it had no effect on their numerous circulating cytokines or peri-renal fat pad mass. AM1241 decreased heart weight and BAT weight; both treatments (AM630 or AM1241) decreased plasma leptin levels, while AM630 also decreased plasma ghrelin and GLP-1 levels. Both treatments decreased Adrb3 and TNF-alpha mRNA levels in eWAT and TNF-alpha levels in pWAT. AM630 treatment also decreased the mRNA levels of Cnr2, leptin, and Slc2a4 in eWAT. In BAT, both treatments decreased leptin, UCP1, and Slc2a4 mRNA levels, with AM1241 also decreasing Adrb3, IL1 beta, and PRDM16 mRNA levels, and AM630 increasing IL6 mRNA levels. In DIO, CB2 agonist and CB2 antagonist treatment reduces circulating leptin in the absence of weight loss and modulates the mRNA responsible for thermogenesis.
Details
- Title
- Treatment of Diet-Induced Obese Rats with CB2 Agonist AM1241 or CB2 Antagonist AM630 Reduces Leptin and Alters Thermogenic mRNA in Adipose Tissue
- Authors
- Lannie O'Keefe (Author) - Victoria UniversityTeresa Vu (Author) - Monash UniversityAnna C. C. Simcocks (Author) - Victoria UniversityKayte A. A. Jenkin (Author) - Victoria UniversityMichael L. L. Mathai (Author) - Florey Institute of Neuroscience and Mental HealthAndrew J. J. McAinch (Author) - Australian Institute for Musculoskeletal ScienceDana S. S. Hutchinson (Corresponding Author) - Monash UniversityDeanne H. H. Hryciw (Author) - Griffith University
- Publication details
- International Journal of Molecular Sciences, Vol.24(8), pp.1-14
- Publisher
- MDPI AG
- Date published
- 2023
- DOI
- 10.3390/ijms24087601
- ISSN
- 1422-0067; 1661-6596
- PMID
- 37108770
- Copyright note
- © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
- Data Availability
- The data presented in this study are available on request from the corresponding author.
- Grant note
- This research was funded by the Allen Foundation, grant number: 2011.385, and A.C.S. was supported by the Australian Rotary Health Scholarship.
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991186523402621
- Output Type
- Journal article
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