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Title:   Author  item
                                            FREIDMAN, ALLON - Indiana University School Of Medicineitem
                                            KIM, JEFFREY - University Of Californiaitem
                                            KAISER, SHAUN - Texas Kidney Instituteitem
                                            PEDERSEN, THERESA - University Of Californiaitem
                                            Newman, Johnitem
                                            WATKINS, BRUCE - University Of California
  Submitted to: American Journal of Kidney Diseases
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 4/1/2016
                                    Publication  Date: 4/1/2016
                                    Citation: Freidman, A.N., Kim, J., Kaiser, S., Pedersen, T., Newman, J.W., Watkins, B.A. 2016. Association between plasma endocannabinoids and appetite in hemodialysis patients: a pilot study. American Journal of Kidney Diseases. 36(7):658-662. doi: 10.1016/j.nutres.2016.03.009.Interpretive Summary: Anorexia is a well-recognized complication of uremia.  This pilot study explored whether circulating endocannabinoids (EC) and EC-like compounds derived from long chain n-6 and n-3 polyunsaturated fatty acids (PUFA) and known to mediate appetite, play a role in influencing appetite in patients with end-stage renal disease.  Therefore we measured blood PUFA and endocannabinoid levels in 9 female hemodialysis patients and 10 healthy controls.  We hypothesized that appetite would be associated with differences in blood levels of EC in hemodialysis patients.  PUFAs were measured in an additional 11 male hemodialysis patients to compare genders.  Appetite was quantified using the validated Simplified Nutritional Appetite Questionnaire (SNAQ) questionnaire.  We observed 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) in female hemodialysis patients compared to controls.  In the female cohort (n=19) correlations between specific EC-like compounds and total SNAQ scores were observed.  Correlations with SNAQ scores were negative for linoleoyl ethanolamide (L-EA; r=-0.529, P<0.05) , positive for the n-3 docosahexaenoic acid-derived EC docosahexaenoyl ethanolamide (DH-EA; r=-0.514, P<0.05), and the L-EA:DH-EA ratio was the strongest SNAQ score predictor (r = 0.755, P=0.001).  Moreover, these changes were most strongly associated with the satiety component of the SNAQ questionnaire. These findings support a link between circulating EC and appetite.  The significance of this relationship and its mediation by dietary PUFA should be explored in future studies.
                                Technical Abstract: Weight loss is a well-recognized complication in subjects undergoing hemodialysis for impaired kidney function.  This pilot study explored whether plasma levels of compounds known to mediate appetite, the endocannabinoids (EC) and EC-like compounds derived from polyunsaturated fatty acids (PUFA), are associated with appetite in patients with end-stage renal disease.  Therefore we measured blood PUFAs and endocannabinoid levels in 9 female hemodialysis patients and 10 healthy controls to test the hypothesus that appetite would increase as these compounds declined in hemodialysis patients.  PUFAs were measured in an additional 11 male hemodialysis patients to compare genders.  Appetite was quantified using the validated Simplified Nutritional Appetite Questionnaire (SNAQ) questionnaire, which uses four simple questions to assess hunger, fullness, food taste, and normal levels of food intake.  We observed 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) in female hemodialysis patients compared to controls.  In the female cohort (n=19) correlations between specific EC-like compounds and total SNAQ scores were observed.  Correlations with SNAQ scores were negative for linoleoyl ethanolamide (L-EA; r=-0.529, P<0.05), positive for the n-3 docosahexaenoic acid-derived EC docosahexaenoyl ethanolamide (DH-EA; r=-0.514, P<0.05), and the L-EA:DH-EA ratio was the strongest SNAQ score predictor (r = 0.755, P=0.001).  Moreover, these changes were most strongly associated with the satiety (i.e. fullness) component of the SNAQ questionnaire. These findings support a link between circulating ECs and appetite.  The significance of this relationship and its mediation by dietary PUFA should be explored in future studies.


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