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.
Hemodialysis patients (HDPs) have higher blood pressure, higher levels of inflammation, a higher risk of cardiovascular disease, and unusually low plasma n-3 polyunsaturated fatty acid (PUFA) levels compared to healthy subjects. The objective of our investigation was to examine the levels of endocannabinoids (eCBs) and oxylipins (OxLs) in female HDPs compared to healthy matched female controls, with the underlying hypothesis that differences in specific PUFA levels in hemodialysis patients would result in changes in eCBs and OxLs. Plasma phospholipid fatty acids were analyzed by gas chromatography. Plasma was extracted and analyzed using ultra-performance liquid chromatography followed by electrospray ionization and tandem MS for eCBs and OxLs. The global untargeted metabolite profiling of plasma was performed by GCTOF MS. Compared to the controls, HDPs showed lower levels of plasma EPA and the associated OxL metabolites 5- and 12-HEPE, 14,15-DiHETE, as well as DHA derived 19(20)-EpDPE. Meanwhile, no changes in arachidonylethanolamide or 2-arachidonylglycerol in the open circulation were detected. Higher levels of multiple N-acylethanolamides, monoacylglycerols, biomarkers of progressive kidney disease, the nitric oxide metabolism-linked citrulline, and the uremic toxins kynurenine and creatine were observed in HDP. These metabolic differences in cCBs and OxLs help explain the severe inflammatory and cardiovascular disease manifested by HDPs, and they should be explored in future studies.
Hemodialysis patients (HDP) have high blood pressure compared to healthy controls and greater incidence of chronic inflammation, higher C‐reactive protein and risk for cardiovascular disease. Moreover, HDP patients typically demonstrate unusually low plasma n‐3 PUFA levels. The purpose of our investigation was to characterize the oxylipins and endocannabinoids in female HDP (55.5 ± 14.2 y, 8.1± 8.4 y on dialysis) and healthy matched controls (54.8 ± 5 y). Plasma was extracted and subsequently analyzed using ultra performance liquid chromatography followed by electrospray ionization and tandem mass spectrometry for oxylipins and endocannabinoids, while RBC and plasma lipid fatty acids were analyzed by GC. HDP showed lower EPA and family related oxylipids 5‐ and 12‐HEPE and 14–15‐ and 17,18‐DiHETE in plasma compared to controls. The potent n‐3 vasodilators 17(18)–EpETrE and 19(20)‐EpDPE were lower in the HDP compared to the controls raising the possibility that hypertension in HDP could in part be due to reduced peripheral vascular relaxation. Further, the levels of 2‐OG, 1‐LG and 2‐LG were higher in HDP compared to the healthy controls. Herein, we report novel findings on oxylipins and endocannabinoids in female HDP that demonstrate differences compared to controls. This research will provide new opportunities to evaluate the role of dietary PUFA in clinical disease in kidney dialysis patients.
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