Adipose tissue endocannabinoid system gene expression: depot differences and effects of diet and exercise

Abstract

BackgroundAlterations of endocannabinoid system in adipose tissue play an important role in lipid regulation and metabolic dysfunction associated with obesity. The purpose of this study was to determine whether gene expression levels of cannabinoid type 1 receptor (CB1) and fatty acid amide hydrolase (FAAH) are different in subcutaneous abdominal and gluteal adipose tissue, and whether hypocaloric diet and aerobic exercise influence subcutaneous adipose tissue CB1 and FAAH gene expression in obese women.MethodsThirty overweight or obese, middle-aged women (BMI = 34.3 ± 0.8 kg/m2, age = 59 ± 1 years) underwent one of three 20-week weight loss interventions: caloric restriction only (CR, N = 9), caloric restriction plus moderate-intensity aerobic exercise (CRM, 45-50% HRR, N = 13), or caloric restriction plus vigorous-intensity aerobic exercise (CRV, 70-75% HRR, N = 8). Subcutaneous abdominal and gluteal adipose tissue samples were collected before and after the interventions to measure CB1 and FAAH gene expression.ResultsAt baseline, FAAH gene expression was higher in abdominal, compared to gluteal adipose tissue (2.08 ± 0.11 vs. 1.78 ± 0.10, expressed as target gene/β-actin mRNA ratio × 10-3, P < 0.05). Compared to pre-intervention, CR did not change abdominal, but decreased gluteal CB1 (Δ = -0.82 ± 0.25, P < 0.05) and FAAH (Δ = -0.49 ± 0.14, P < 0.05) gene expression. CRM or CRV alone did not change adipose tissue CB1 and FAAH gene expression. However, combined CRM and CRV (CRM+CRV) decreased abdominal adipose tissue FAAH gene expression (Δ = -0.37 ± 0.18, P < 0.05). The changes in gluteal CB1 and abdominal FAAH gene expression levels in the CR alone and the CRM+CRV group were different (P < 0.05) or tended to be different (P = 0.10).ConclusionsThere are depot differences in subcutaneous adipose tissue endocannabinoid system gene expression in obese individuals. Aerobic exercise training may preferentially modulate abdominal adipose tissue endocannabinoid-related gene expression during dietary weight loss.Trial RegistrationClinicalTrials.gov: NCT00664729.

Exercise as an adjunctive treatment for cannabis use disorder

“…Almost no research has been conducted to directly examine the effects of chronic exercise training on the eCB system in humans, and the few studies that have examined eCB levels as a secondary aim of their projects have found conflicting results (46–49). Relevant to its presence in reward-processing brain regions, though, one study found that plasma AEA concentrations were significantly lower at baseline, after acute exercise, and after 2 weeks of inactivity in runners categorized as “exercise dependent” (based on the Exercise Dependence Scale, which incorporates the DSM-IV criteria for substance abuse and dependence) compared to runners who did not meet the criteria for exercise dependence (50).…”

Moderate-Vigorous Physical Activity across Body Mass Index in Females: Moderating Effect of Endocannabinoids and Temperament

“…You et al [21] found that the gene expression of fatty acid amide hydrolase (FAAH), enzyme that degrades the N-acyl-ethanolamides, is lower in the abdominal adipose of obese women on a program combining exercise training and a caloric restriction diet. Dubreucq et al [22] reported CB1 knockout mice to display 30–40% less running behavior, and proposed a functional loop between the eCB system and MVPA.…”

Role of bioactive lipid mediators in obese adipose tissue inflammation and endocrine dysfunction

“…In visceral adipose tissue there is greater mRNA expression of CB-1 than in subcutaneous adipose tissue (Bluher et al, 2006). Moreover, in obese individuals, 2-AG, CB-1 and MGL are up-regulated in abdominal adipose tissue, whereas their expression is downregulated in gluteal adipose tissue (Pagano et al, 2007;You et al, 2011). Collectively, current evidence indicates that the endocannabinoid system is dysregulated in obesity and greatly influences the storage of energy in different adipose tissue depots.…”

“…The expression of the CB-1 receptor is also correlated with BMI and the metabolic syndrome (Sarzani et al, 2009). Overall the endocannabinoid system is dysregultaed in peripheral tissues in obesity, altering lipid and glucose metabolism (Pagano et al, 2007;You et al, 2011;Izzo et al, 2009). In visceral adipose tissue there is greater mRNA expression of CB-1 than in subcutaneous adipose tissue (Bluher et al, 2006).…”