Association between plasma endocannabinoids and appetite in hemodialysis patients: A pilot study

Abstract

Uremia-associated anorexia may be related to altered levels of long chain n-6 and n-3 polyunsaturated fatty acid (PUFA) derived circulating endocannabinoids (EC) and EC-like compounds that are known to mediate appetite. Our study's hypothesis was that such molecules are associated with appetite in patients with end-stage renal disease. A cross-sectional observational study was performed in 20 chronic hemodialysis patients (9 females, 11 males) and 10 healthy female controls in whom appetite was assessed using the Simplified Nutritional Appetite Questionnaire (SNAQ) and blood drawn in the fasting (and when applicable) pre-dialysis state. Blood levels of PUFA and EC were also measured. Higher blood levels of the long chain n-6 fatty acid 20:4n6 (arachidonic acid) and lower levels of the long chain n-3 fatty acid 20:5n3 (eicosapentaenoic acid) were observed in female hemodialysis patients compared to controls. No differences were observed between male and female patients. In female study participants strong correlations between specific EC-like compounds and total SNAQ scores were noted, including with the n-6 PUFA derived linoleoyl ethanolamide (L-EA; ρ= -0.60, P<0.01) and the n-3 PUFA derived docosahexaenoyl ethanolamide (DH-EA; ρ= 0.63, P<0.01). The L-EA:DH-EA ratio was most strongly associated with the SNAQ score (ρ= -0.74, P≤0.001), and its questions associated with appetite (ρ= -0.69, P≤0.01) and satiety (ρ= -0.81, P≤0.001). These findings support a link between circulating EC and appetite in hemodialysis patients.

Serum Endocannabinoid Levels in Patients With End-Stage Renal Disease

“…In this regard, data on the association of endocannabinoids with clinical and laboratory markers are very limited in patients with ESRD. The only available report is a study by Friedman et al [23] , which did not find any differences in plasma (EDTA-preserved tubing) endocannabinoid levels between healthy controls and patients with ESRD. However, it should be noted that the small sample size (n = 20), significant sex differences between the control and ESRD groups, and use of plasma (vs our samples which were serum) in their study make interpretation and comparison with our study difficult [23].…”

“…The only available report is a study by Friedman et al [23] , which did not find any differences in plasma (EDTA-preserved tubing) endocannabinoid levels between healthy controls and patients with ESRD. However, it should be noted that the small sample size (n = 20), significant sex differences between the control and ESRD groups, and use of plasma (vs our samples which were serum) in their study make interpretation and comparison with our study difficult [23]. Our study evaluated serum endocannabinoid levels in a large cohort of patients with ESRD who were compared with age- and sex-matched healthy controls.…”

“…However, it is also important to recognize that clear mechanisms that can account for these differential changes need to be examined in future studies in order to delineate the possible causes of these observations. In addition, future studies will need to address the potential differences between serum and plasma levels of these lipid-derived mediators, given the distinctions noted in our studies compared with findings of the other investigation [23].…”

Food reward from a behavioural and (neuro)physiological perspective

“…It has been suggested that plasma endocannabinoids are a result of spill-over from tissues like the brain and gut (Hill et al, 2008;Matias et al, 2012), however, it is unknown to what extent plasma concentrations reflect endocannabinoid concentrations in these other tissues. A previous study suggested a link between plasma endocannabinoid concentration and feelings of appetite (Friedman et al, 2016).…”

“…These markers should respond to nutrient and caloric intake, but not to the palatability of the food. To further elucidate the post-ingestive endocannabinoid response, we not only measured AEA, 2-AG, OEA and PEA, but included three more endocannabinoid-related compounds that have been suggested to be relevant for food intake or induce cannabinomimetic behavioural effects, namely stearoylethanolamide (SEA; Terrazzino et al, 2004), dihomo-γ-linolenoylethanolamide (DLE; Barg et al, 1995), and docosahexaenoylethanolamide (DHEA; Barg et al, 1995;Friedman et al, 2016).…”