Endocannabinoid Responses To Aerobic, Resistance, Or Combined Exercise In Adults With And Without Metabolic Syndrome

PURPOSE: Endocannabinoid (eCB) dysfunction contributes to the progression of cardiometabolic disease. Exercise may improve cardiometabolic outcomes through its effects on the eCB system, although there are limited data from large exercise trials. This study compared the effects of 1 year of aerobic (AE), resistance (RE), or combined aerobic and resistance exercise training (CE) on circulating eCB concentrations in adults with and without metabolic syndrome (MetS). METHODS: Participants were 406 inactive adults (53% women, 35-70 years), and 167 had MetS. They were randomly assigned to AE only (n = 101), RE only (n = 102), CE (n = 101), or a no-exercise control group (CON) (n = 102). Participants performed supervised exercise 3 times/week, 60 min/session (CE performed 30 min each of AE and RE), at 50-80% of their maximum intensity. Fasted blood samples were collected at baseline and 1 year. Linear mixed effects models following intention-to-treat assessed 1-year changes eCBs N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) while adjusting for age, sex, and baseline values. Subgroup analyses were performed among participants with and without MetS. RESULTS: Overall, 94% of participants completed the study with an 82% exercise attendance rate. Baseline eCBs were not different between groups (p > .05), although AEA (p = .005) and 2-AG (p < .0001) were higher at baseline among MetS participants. There were no group-by-time interactions for changes in AEA (p = .49) or 2-AG (p = .41). There were also no interactions for changes in AEA or 2-AG in participants with (AEA p = .21; 2-AG p = .66) or without MetS (AEA p = .63; 2-AG p = .51). There were no correlations between changes in eCBs and changes in individual MetS risk factors (e.g., waist circumference, blood pressure, glucose, triglycerides, or cholesterol; all ps > .05). CONCLUSION: These results suggest that unlike acute exercise, long-term exercise training does not modify circulating eCB concentrations in middle-aged adults, although a more complete profiling of the eCB system (e.g., eCB receptor expression) in the context of exercise training and cardiometabolic outcomes is needed. Supported by NIH Grants R21DK131429 (Brellenthin) and R01HL133069 (Lee).