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Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1α pathway.
Biochem Biophys Res Commun. 2013 Jul 05; 436(3):377-81.BB

Abstract

Abnormal fatty acid oxidation has been associated with obesity and type 2 diabetes. At the transcriptional level, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) has been reported to strongly increase the ability of hormone nuclear receptors PPARα and ERRα to drive transcription of fatty acid oxidation enzymes. In this study, we report that a specific agonist of the type 2 cannabinoid receptor (CB2R) can lead to fatty acid oxidation through the PGC-1α pathway. We have found that CB2R is expressed in differentiated C2C12 myotubes, and that use of the specific agonist trans-caryophyllene (TC) stimulates sirtuin 1 (SIRT1) deacetylase activity by increasing the phosphorylation of cAMP response element-binding protein (CREB), thus leading to increased levels of PGC-1α deacetylation. This use of TC treatment increases the expression of genes linked to the fatty acid oxidation pathway in a SIRT1/PGC-1α-dependent mechanism and also drastically accelerates the rate of complete fatty acid oxidation in C2C12 myotubes, neither of which occur when CB2R mRNA is knocked down using siRNA. These results reveal that activation of CB2R by a selective agonist promotes lipid oxidation through a signaling/transcriptional pathway. Our findings imply that pharmacological manipulation of CB2R may provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation.

Authors+Show Affiliations

Department of Endocrinology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23747418

Citation

Zheng, Xuqin, et al. "Activation of Type 2 Cannabinoid Receptors (CB2R) Promotes Fatty Acid Oxidation Through the SIRT1/PGC-1α Pathway." Biochemical and Biophysical Research Communications, vol. 436, no. 3, 2013, pp. 377-81.
Zheng X, Sun T, Wang X. Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1α pathway. Biochem Biophys Res Commun. 2013;436(3):377-81.
Zheng, X., Sun, T., & Wang, X. (2013). Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1α pathway. Biochemical and Biophysical Research Communications, 436(3), 377-81. https://doi.org/10.1016/j.bbrc.2013.05.108
Zheng X, Sun T, Wang X. Activation of Type 2 Cannabinoid Receptors (CB2R) Promotes Fatty Acid Oxidation Through the SIRT1/PGC-1α Pathway. Biochem Biophys Res Commun. 2013 Jul 5;436(3):377-81. PubMed PMID: 23747418.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of type 2 cannabinoid receptors (CB2R) promotes fatty acid oxidation through the SIRT1/PGC-1α pathway. AU - Zheng,Xuqin, AU - Sun,Tao, AU - Wang,Xiaodong, Y1 - 2013/06/04/ PY - 2013/05/24/received PY - 2013/05/25/accepted PY - 2013/6/11/entrez PY - 2013/6/12/pubmed PY - 2013/9/10/medline KW - Fatty acid oxidation KW - Peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) KW - Sirtuin 1 (Sirt1) KW - Trans-caryophyllene KW - Type 2 cannabinoid receptor (CB2R) SP - 377 EP - 81 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 436 IS - 3 N2 - Abnormal fatty acid oxidation has been associated with obesity and type 2 diabetes. At the transcriptional level, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) has been reported to strongly increase the ability of hormone nuclear receptors PPARα and ERRα to drive transcription of fatty acid oxidation enzymes. In this study, we report that a specific agonist of the type 2 cannabinoid receptor (CB2R) can lead to fatty acid oxidation through the PGC-1α pathway. We have found that CB2R is expressed in differentiated C2C12 myotubes, and that use of the specific agonist trans-caryophyllene (TC) stimulates sirtuin 1 (SIRT1) deacetylase activity by increasing the phosphorylation of cAMP response element-binding protein (CREB), thus leading to increased levels of PGC-1α deacetylation. This use of TC treatment increases the expression of genes linked to the fatty acid oxidation pathway in a SIRT1/PGC-1α-dependent mechanism and also drastically accelerates the rate of complete fatty acid oxidation in C2C12 myotubes, neither of which occur when CB2R mRNA is knocked down using siRNA. These results reveal that activation of CB2R by a selective agonist promotes lipid oxidation through a signaling/transcriptional pathway. Our findings imply that pharmacological manipulation of CB2R may provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/23747418/Activation_of_type_2_cannabinoid_receptors__CB2R__promotes_fatty_acid_oxidation_through_the_SIRT1/PGC_1α_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(13)00915-7 DB - PRIME DP - Unbound Medicine ER -