DHA dampens endocannabinoid tone related to cannabinoid receptor expression in proliferating C2C12 myoblasts

Abstract

Emerging evidence indicates that the peripheral endocannabinoid signaling system (ECS) has a pronounced effect on health status, specifically glucose homeostasis. Focus on skeletal muscle is of great interest as it is a major storage for glycogen in the body. However, overactivation of the ECS in skeletal muscle has been shown to diminish insulin sensitivity. In particular, an elevation of CB1 activity has been reported in diabetic rodent models. Our research intends to identify changes in ECS tone by fatty acid (FA) enrichment. Proliferating C2C12 myoblasts were cultured until 50% confluency and treated with either 25 μM of AA, EPA, AEA, 2‐AG, or a BSA control for 24 h. Cells were collected and labeled with antibodies for CB1 and CB2 for FACS flow cytometry and FA analysis by GC. Compared to the control, FACS revealed a significant reduction in CB1 abundance with DHA treatment, while a significantly higher expression of CB1 was found with AA. No difference in CB2 level was observed. FA composition of myoblasts reflected their respective FA treatment. Interestingly, between the two AA‐derived ECS ligands, only 2‐AG enrichment had a doubling of its precursor, AA, but not with AEA. These findings suggest that DHA may dampen an overactive EC tone.Grant Funding Source: Diet and Health Initiative, UConn, Storrs, CT, USA