Abstract
Background/ObjectivesEndocannabinoids (ECs) are associated with obesity and ectopic fat accumulation, both of which play a role in the development of cardiovascular disease (CVD) in type 2 diabetes (T2D). The effect of prolonged caloric restriction on ECs in relation to fat distribution and cardiac function is still unknown. Therefore, our aim was to investigate this relationship in obese T2D patients with coronary artery disease (CAD).Subjects/MethodsIn a prospective intervention study, obese T2D patients with CAD (n = 27) followed a 16 week very low calorie diet (VLCD; 450–1000 kcal/day). Cardiac function and fat accumulation were assessed with MRI and spectroscopy. Plasma levels of lipid species, including ECs, were measured using liquid chromatography-mass spectrometry.ResultsVLCD decreased plasma levels of virtually all measured lipid species of the class of N-acylethanolamines including the EC anandamide (AEA; −15%, p = 0.016), without decreasing monoacylglycerols including the EC 2-arachidonoylglycerol (2-AG). Baseline plasma AEA levels strongly correlated with the volume of subcutaneous white adipose tissue (SAT; R2 = 0.44, p < 0.001). VLCD decreased the volume of SAT (−53%, p < 0.001), visceral white adipose tissue (VAT) (−52%, p < 0.001), epicardial white adipose tissue (−15%, p < 0.001) and paracardial white adipose tissue (−28%, p < 0.001). VLCD also decreased hepatic (−86%, p < 0.001) and myocardial (−33%, p < 0.001) fat content. These effects were accompanied by an increased left ventricular ejection fraction (54.8 ± 8.7–56.2 ± 7.9%, p = 0.016).ConclusionsCaloric restriction in T2D patients with CAD decreases AEA levels, but not 2-AG levels, which is paralleled by decreased lipid accumulation in adipose tissue, liver and heart, and improved cardiovascular function. Interestingly, baseline AEA levels strongly correlated with SAT volume. We anticipate that dietary interventions are worthwhile strategies in advanced T2D, and that reduction in AEA may contribute to the improved cardiometabolic phenotype induced by weight loss.
Highlights
The endocannabinoid (EC) system is a key player in Center (LUMC), Leiden, The Netherlands 2Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center (LUMC), Leiden, The lipid and glucose metabolism and in regulation of energy balance[1]
very low calorie diet (VLCD) decreased the volume of subcutaneous white adipose tissue (SAT) (−53%, p < 0.001), visceral white adipose tissue (VAT) (−52%, p < 0.001), epicardial white adipose tissue (−15%, p < 0.001) and paracardial white adipose tissue (−28%, p < 0.001)
Caloric restriction in type 2 diabetes (T2D) patients with coronary artery disease (CAD) decreases acylethanolamines including the EC anandamide (AEA) levels, but not 2-AG levels, which is paralleled by decreased lipid accumulation in adipose tissue, liver and heart, and improved cardiovascular function
Summary
The endocannabinoid (EC) system is a key player in Center (LUMC), Leiden, The Netherlands 2Einthoven Laboratory for Experimental Vascular Medicine, LUMC, Leiden, The lipid and glucose metabolism and in regulation of energy balance[1] It consists of the cannabinoid receptors type 1. Binding of ECs to the cannabinoid receptors results in various metabolic effects, including increased food intake, enhanced lipogenesis and reduced energy expenditure[2,3] This is supported by several studies reporting strong associations between high plasma EC levels and triglycerides (TG), intra-abdominal obesity and insulin resistance in obese and type 2 diabetes (T2D) patients[4,5,6,7]. Elevated levels of ECs can contribute to relative insulin deficiency and to accumulation of visceral adipose tissue (VAT) and obesity, and as such may have a causal role in the pathophysiology of T2D and CVD3
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
