Treatment of Diet-Induced Obese Rats with CB<sub>2</sub> Agonist AM1241 or CB<sub>2</sub> Antagonist AM630 Reduces Leptin and Alters Thermogenic mRNA in Adipose Tissue
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 (CB<sub>2</sub>) contributing to the inflammatory response. The effects of modulating CB<sub>2</sub> w...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7601 |
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| author | Lannie O’Keefe Teresa Vu Anna C. Simcocks Kayte A. Jenkin Michael L. Mathai Andrew J. McAinch Dana S. Hutchinson Deanne H. Hryciw |
| author_facet | Lannie O’Keefe Teresa Vu Anna C. Simcocks Kayte A. Jenkin Michael L. Mathai Andrew J. McAinch Dana S. Hutchinson Deanne H. Hryciw |
| author_sort | Lannie O’Keefe |
| collection | DOAJ |
| description | 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 (CB<sub>2</sub>) contributing to the inflammatory response. The effects of modulating CB<sub>2</sub> 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 CB<sub>2</sub> agonism and CB<sub>2</sub> 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-α mRNA levels in eWAT and TNF-α 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, IL1β, and PRDM16 mRNA levels, and AM630 increasing IL6 mRNA levels. In DIO, CB<sub>2</sub> agonist and CB<sub>2</sub> antagonist treatment reduces circulating leptin in the absence of weight loss and modulates the mRNA responsible for thermogenesis. |
| first_indexed | 2024-03-11T04:55:28Z |
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| id | doaj.art-c6e772281c25416f8d1a80bd1c94ef3b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:55:28Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c6e772281c25416f8d1a80bd1c94ef3b2023-11-17T19:43:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248760110.3390/ijms24087601Treatment of Diet-Induced Obese Rats with CB<sub>2</sub> Agonist AM1241 or CB<sub>2</sub> Antagonist AM630 Reduces Leptin and Alters Thermogenic mRNA in Adipose TissueLannie O’Keefe0Teresa Vu1Anna C. Simcocks2Kayte A. Jenkin3Michael L. Mathai4Andrew J. McAinch5Dana S. Hutchinson6Deanne H. Hryciw7Institute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, AustraliaInstitute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, AustraliaInstitute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, AustraliaInstitute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, AustraliaInstitute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, AustraliaInstitute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, AustraliaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, AustraliaInstitute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, VIC 8001, AustraliaDiet-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 (CB<sub>2</sub>) contributing to the inflammatory response. The effects of modulating CB<sub>2</sub> 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 CB<sub>2</sub> agonism and CB<sub>2</sub> 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-α mRNA levels in eWAT and TNF-α 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, IL1β, and PRDM16 mRNA levels, and AM630 increasing IL6 mRNA levels. In DIO, CB<sub>2</sub> agonist and CB<sub>2</sub> antagonist treatment reduces circulating leptin in the absence of weight loss and modulates the mRNA responsible for thermogenesis.https://www.mdpi.com/1422-0067/24/8/7601diet-induced obesity (DIO)inflammationendocannabinoid system (ECS)AM1241AM630adipose tissue |
| spellingShingle | Lannie O’Keefe Teresa Vu Anna C. Simcocks Kayte A. Jenkin Michael L. Mathai Andrew J. McAinch Dana S. Hutchinson Deanne H. Hryciw Treatment of Diet-Induced Obese Rats with CB<sub>2</sub> Agonist AM1241 or CB<sub>2</sub> Antagonist AM630 Reduces Leptin and Alters Thermogenic mRNA in Adipose Tissue International Journal of Molecular Sciences diet-induced obesity (DIO) inflammation endocannabinoid system (ECS) AM1241 AM630 adipose tissue |
| title | Treatment of Diet-Induced Obese Rats with CB<sub>2</sub> Agonist AM1241 or CB<sub>2</sub> Antagonist AM630 Reduces Leptin and Alters Thermogenic mRNA in Adipose Tissue |
| title_full | Treatment of Diet-Induced Obese Rats with CB<sub>2</sub> Agonist AM1241 or CB<sub>2</sub> Antagonist AM630 Reduces Leptin and Alters Thermogenic mRNA in Adipose Tissue |
| title_fullStr | Treatment of Diet-Induced Obese Rats with CB<sub>2</sub> Agonist AM1241 or CB<sub>2</sub> Antagonist AM630 Reduces Leptin and Alters Thermogenic mRNA in Adipose Tissue |
| title_full_unstemmed | Treatment of Diet-Induced Obese Rats with CB<sub>2</sub> Agonist AM1241 or CB<sub>2</sub> Antagonist AM630 Reduces Leptin and Alters Thermogenic mRNA in Adipose Tissue |
| title_short | Treatment of Diet-Induced Obese Rats with CB<sub>2</sub> Agonist AM1241 or CB<sub>2</sub> Antagonist AM630 Reduces Leptin and Alters Thermogenic mRNA in Adipose Tissue |
| title_sort | treatment of diet induced obese rats with cb sub 2 sub agonist am1241 or cb sub 2 sub antagonist am630 reduces leptin and alters thermogenic mrna in adipose tissue |
| topic | diet-induced obesity (DIO) inflammation endocannabinoid system (ECS) AM1241 AM630 adipose tissue |
| url | https://www.mdpi.com/1422-0067/24/8/7601 |
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