Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice
Cannabis use stimulates calorie intake, but epidemiological studies show that people who regularly use it are leaner than those who don’t. Two explanations have been proposed for this paradoxical finding. One posits that Δ<sup>9</sup>-tetrahydrocannabinol (THC) in cannabis desensitizes a...
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MDPI AG
2024-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/5/461 |
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| author | Kwang-Mook Jung Lin Lin Daniele Piomelli |
| author_facet | Kwang-Mook Jung Lin Lin Daniele Piomelli |
| author_sort | Kwang-Mook Jung |
| collection | DOAJ |
| description | Cannabis use stimulates calorie intake, but epidemiological studies show that people who regularly use it are leaner than those who don’t. Two explanations have been proposed for this paradoxical finding. One posits that Δ<sup>9</sup>-tetrahydrocannabinol (THC) in cannabis desensitizes adipose CB1 cannabinoid receptors, stopping their stimulating effects on lipogenesis and adipogenesis. Another explanation is that THC exposure in adolescence, when habitual cannabis use typically starts, produces lasting changes in the developing adipose organ, which impacts adult systemic energy use. Here, we consider these possibilities in the light of a study which showed that daily THC administration in adolescent mice produces an adult metabolic phenotype characterized by reduced fat mass, partial resistance to obesity and dyslipidemia, and impaired thermogenesis and lipolysis. The phenotype, whose development requires activation of CB1 receptors in differentiated adipocytes, is associated with overexpression of myocyte proteins in the adipose organ with unchanged CB1 expression. We propose that adolescent exposure to THC causes lasting adipocyte dysfunction and the consequent emergence of a metabolic state that only superficially resembles healthy leanness. A corollary of this hypothesis, which should be addressed in future studies, is that CB1 receptors and their endocannabinoid ligands may contribute to the maintenance of adipocyte differentiation during adolescence. |
| first_indexed | 2024-04-25T00:33:42Z |
| format | Article |
| id | doaj.art-c21f823c85a947308c7e2133b2f16cf3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-25T00:33:42Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c21f823c85a947308c7e2133b2f16cf32024-03-12T16:41:48ZengMDPI AGCells2073-44092024-03-0113546110.3390/cells13050461Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in MiceKwang-Mook Jung0Lin Lin1Daniele Piomelli2Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697, USADepartment of Anatomy and Neurobiology, University of California, Irvine, CA 92697, USADepartment of Anatomy and Neurobiology, University of California, Irvine, CA 92697, USACannabis use stimulates calorie intake, but epidemiological studies show that people who regularly use it are leaner than those who don’t. Two explanations have been proposed for this paradoxical finding. One posits that Δ<sup>9</sup>-tetrahydrocannabinol (THC) in cannabis desensitizes adipose CB1 cannabinoid receptors, stopping their stimulating effects on lipogenesis and adipogenesis. Another explanation is that THC exposure in adolescence, when habitual cannabis use typically starts, produces lasting changes in the developing adipose organ, which impacts adult systemic energy use. Here, we consider these possibilities in the light of a study which showed that daily THC administration in adolescent mice produces an adult metabolic phenotype characterized by reduced fat mass, partial resistance to obesity and dyslipidemia, and impaired thermogenesis and lipolysis. The phenotype, whose development requires activation of CB1 receptors in differentiated adipocytes, is associated with overexpression of myocyte proteins in the adipose organ with unchanged CB1 expression. We propose that adolescent exposure to THC causes lasting adipocyte dysfunction and the consequent emergence of a metabolic state that only superficially resembles healthy leanness. A corollary of this hypothesis, which should be addressed in future studies, is that CB1 receptors and their endocannabinoid ligands may contribute to the maintenance of adipocyte differentiation during adolescence.https://www.mdpi.com/2073-4409/13/5/461cannabisadolescencetrans-differentiationadipocyte |
| spellingShingle | Kwang-Mook Jung Lin Lin Daniele Piomelli Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice Cells cannabis adolescence trans-differentiation adipocyte |
| title | Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice |
| title_full | Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice |
| title_fullStr | Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice |
| title_full_unstemmed | Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice |
| title_short | Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice |
| title_sort | overactivation of the endocannabinoid system in adolescence disrupts adult adipose organ function in mice |
| topic | cannabis adolescence trans-differentiation adipocyte |
| url | https://www.mdpi.com/2073-4409/13/5/461 |
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