receptor a la serotonina (subtipo 5-HT2c) se vuelven obesos a consecuencia de un incremento importante de su ingesta.27 Este y otros descubrimientos28-30 contribuyen a enfatizar el papel de los receptores 5-HT2c en el control de la ingesta y la saciedad, así como la importancia de la disponibilidad plasmática de triptófano. Cowen et al.,10 intentando responder a la pregunta «–por qué es tan difícil hacer dieta», mostraba que hacer dieta no sólo provoca una disminución en la disponibilidad de triptófano en el cerebro sino que produce, además, un incremento compensatorio de la sensibilidad de los receptores 5-HT2c. Se piensa que el comportamiento alimentario compulsivo31 se ve precipitado por una reducción de la actividad serotoninérgica en el cerebro y que la utilización clínica de drogas que antagonicen a dichos receptores justificaría los episodios de bulimia nerviosa que experimentan los pacientes durante el tratamiento de restricción calórica, que comprometen su continuación.Otra evidencia a favor de que un bajo valor de la relación TRP/LNAA incrementa la sensación de hambre en humanos es la correlación positiva entre el cómputo de los episodios de hambre y la relación TRP/LNAA descripta en pacientes diabéticos en ayunas.12,32Cabe esperar que una disponibilidad reducida de triptófano crónica (tal y como ocurre en la obesidad humana) comprometa seriamente la restricción calórica voluntaria. Así, aceptando que la relación plasmática TRP/LNAA refleja la estimulación de la vía serotoninérgica de la saciedad, puede sugerirse que hacer dieta per se sería particularmente difícil y contraproducente en individuos obesos, más aún a medida que aumenta el valor del IMC y más difícil en hombres obesos que en mujeres obesas.AgradecimientosAgradecemos al Dr. Enric Benito del Hospital General de Mallorca (Consell Insular de Mallorca), Macié Tomés y Manuel Díaz-González del Departamento de Medicina de EMAYA (Ayuntamiento de Palma de Mallorca), Ana García del Hospital de Son Dureta (INSALUD), Leopoldo Mir del Residencia de Ancianos (Consell Insular de Mallorca) y Abelard Corrales del Centro de Salud del Camp Redó (INSALUD), el que nos hayan proporcionado las muestras de sangre que han permitido llevar a cabo este trabajo. También agradecemos a Jordi Pericás la asistencia técnica prestada.************************************************************(TITULO PARA LA TABLA -VA EN LA PARTE SUPERIOR- Y EPIGRAFE DE LA FIGURA -VA EN LA PARTE INFERIOR-) Tabla 1. Niveles plasmáticos de triptófano (TRP) y aminoácidos neutros de cadena larga (LNAA) y valores de la relación TRP/LNAA en hombres y mujeres con diferente grado de obesidad (normopeso, con sobrepeso obesos). Correlaciones entre la relación TRP/LNAA y el índice de masa corporal (IMC = kg/m2) en hombres (n = 42) y mujeres (n = 46).************************************************************ Bibliografía1. Fernstrom JD: Diet, food intake regulation, and brain serotonin: An overview; en Bray GA and Ryan DH (eds): The Science of Food Regulation. Lousiana State University Press, 1992, vol 2, pp 195-209.2. Pijl H, Koppeschaar HPF, Cohen AF, Iestra JA, Shoemaker HC, Frölich M, Onkenhout W, Meinders AE: Evidence for brain serotonin-mediated control of carbohydrate consumption in normal weight and obese humans. Int J Obesity 1993; 17: 513-520.3. Lieberman HR, Caballero B, Finer N: The composition of lunch determines afternoon plasma tryptophan ratios in humans. J Neural Transm 1986; 65 (Suppl. 3-4): 211-217.4. Blundell JE, Lawton CL, Halford JC: Serotonin, eating behavior, and fat intake. Obes Res 1995; 3 (Suppl. 4): 471S-476S.5. Markus CR, Olivier B, Panhuysen GE, Van Der Gugten J, Alles MS, Tuiten A, Westenberg HG, Fekkes D, Koppeschaar HF, de Haan EE: The bovine protein alpha-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress. Am J Clin Nutr 2000, 71: 1536-15446. Fernstrom JD, Wurtman RJ: Brain serotonin content: increase following ingestion of carbohydrate diet. Science 1971; 174: 1023-1025.7. Lawton CL, Wales JK, Hill AJ, Blundell JE: Serotoninergic manipulation, meal-induced satiety and eating pattern: effect of fluoxetine in obese female subjects. Obes Res 1995; 3: 345-356.8. Swann AC, Johnson BA, Cloninger CR, Chen YR: Relationships of plasma tryptophan availability to course of illness and clinical features of alcoholism: a preliminary study. Psychopharmacology 143, 380-384, 1999.9. Wurtman RJ, Wurtman JJ: Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res 1995; 3 (Suppl. 4): 477S-480S.10. Cowen PJ, Clifford EM, Williams C, Walsh AES, Fairburn CG: Why is dieting so difficult. Nature 1995; 376: 557.11. Wolfe BE, Metzger ED, Stollar C: The effects of dieting on plasma tryptophan concentration and food intake in healthy women. Physiol Behav 1997; 61 (Suppl. 4): 537-541.12. Wolever TM, Jenkins DJ, Josse RG, Wong GS, Lee R, Anderson GH: Relationship between fasting serum tryptophan/large neutral amino acid ratio and reported hunger in subjects with diabetes. Diabetes Res 1988; 9 (Suppl. 3): 131-137.13. Serra F, Picó C, Johnston J, Carnie J, Palou A. Opposite response to starvation of TRP/LNAA ratio in lean and obese Zucker rats. Biochem Mol Biol Int 1993; 29 (Suppl 3): 483-491.14. Italian Consensus Conference: Overweight, Obesity and Health. Rome, 5 y 6 abril 1991.15. Picó C, Pons A, Palou A: A significant pool of amino acids is adsorbed on blood cell membranes. Biosci Rep 1991; 11: 223-230.16. Arola Ll, Herrera E, Alemany M. A new method of deproteinization of small samples of blood plasma for amino acid determination. Anal Biochem 1977; 82: 236-239.17. Bidlingmeyer BA, Cohen SA, Tarvin TL: Rapid analysis of amino acids using pre-column derivatization. J Chromatogr 1984; 336: 93-104.18. Armstrong MD, Stave U: A study of plasma free amino acid levels. II. Normal values for children and adults. Metabolism 1973a; 22: 561-569.19. Armstrong MD, Stave U. A study of plasma free amino acid levels. III. Variations during growth and aging. Metabolism 1973b; 22: 571-578.20. Björnesjö KB: The distribution of alpha amino nitrogen, urea nitrogen, and non protein nitrogen between erythrocytes and plasma in healthy males and females. Scand J Clin Lab Invest 1963; 15: 25-37.21. Milsom JP, Morgan MY, Sherlock S: Factors affecting plasma amino acid concentrations in control subjects. Metabolism 1979; 28: 313-319.22. 23. Craft IL, Peters TJ: Quantitative changes in plasma amino acids induced by oral contraceptives. Clin Sci 1971; 41: 301-307.24. Proenza AM, Roca P, Virgili J, Remesar X, Alemany M, Palou A: Estrogen effects on blood amino acid compartmentation. Life Sci 1995; 57 (Suppl 17): 1589-1597.25. Björntorp P: Metabolic implications of body fat distribution. Diabetes Care 1991; 14: 1132-1143.26. Krotkiewski M, Björntorp P, Sjöström L, Smith U: Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest 1983; 72: 1150-1162.27. Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman M. F, Julius D: Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 1995; 374: 542-546.28. Fernstrom MH, Fernstrom JD: Brain tryptophan concentrations and serotonin synthesis remain responsive to food consumption after the ingestion of sequential meals. Am J Clin Nutr 1995; 61 (Suppl. 2): 312-319.29. Pijl H., Cohen AF, Verkes RJ, Koppeschaar HPF, Iestra JA, Shoemaker HC, Frölich M, Onkenhout W, Meinders AE: Plasma amino acid ratios related to brain serotonin synthesis in response to food intake in bulimia nervosa. Biol Psychiatry 1995; 38 (Suppl. 10): 659-668.30. Spedding M, Ouvry C, Millan M, Duhault J, Dacquet C: Neural control of dieting. Nature 1996; 380: 488.31. Fluoxetine Bulimia Nervosa Collaborative Study Group. Fluoxetine in the treatment of bulimia nervosa: A multicenter, placebo-controlled, double-blind trial. Arch Gen Psychiatry 1992; 49: 139-147.32. Noach EL: Appetite regulation by serotoninergic mechanisms and effects of d-fenfluramine. Neth J Med 1994; 45 (Suppl. 3): 123-133. (INSALU, el que nos hayan proporcionado las muestras de sangre que han permitido llevar a cabo este trabajo. También agradecemos a Jordi Pericás la asistencia técnica prestada.************************************************************(TITULO PARA LA TABLA -VA EN LA PARTE SUPERIOR- Y EPIGRAFE DE LA FIGURA -VA EN LA PARTE INFERIOR-)Tabla 1. Niveles plasmáticos de triptófano (TRP) y aminoácidos neutros de cadena larga (LNAA) y valores de la relación TRP/LNAA en hombres y mujeres con diferente grado de obesidad (normopeso, con sobrepeso obesos). Correlaciones entre la relación TRP/LNAA y el índice de masa corporal (IMC = kg/m2) en hombres (n = 42) y mujeres (n = 46).************************************************************ Bibliografía1. Fernstrom JD: Diet, food intake regulation, and brain serotonin: An overview; en Bray GA and Ryan DH (eds): The Science of Food Regulation. Lousiana State University Press, 1992, vol 2, pp 195-209.2. Pijl H, Koppeschaar HPF, Cohen AF, Iestra JA, Shoemaker HC, Frölich M, Onkenhout W, Meinders AE: Evidence for brain serotonin-mediated control of carbohydrate consumption in normal weight and obese humans. Int J Obesity 1993; 17: 513-520.3. Lieberman HR, Caballero B, Finer N: The composition of lunch determines afternoon plasma tryptophan ratios in humans. J Neural Transm 1986; 65 (Suppl. 3-4): 211-217.4. Blundell JE, Lawton CL, Halford JC: Serotonin, eating behavior, and fat intake. Obes Res 1995; 3 (Suppl. 4): 471S-476S.5. Markus CR, Olivier B, Panhuysen GE, Van Der Gugten J, Alles MS, Tuiten A, Westenberg HG, Fekkes D, Koppeschaar HF, de Haan EE: The bovine protein alpha-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress. Am J Clin Nutr 2000, 71: 1536-15446. Fernstrom JD, Wurtman RJ: Brain serotonin content: increase following ingestion of carbohydrate diet. Science 1971; 174: 1023-1025.7. Lawton CL, Wales JK, Hill AJ, Blundell JE: Serotoninergic manipulation, meal-induced satiety and eating pattern: effect of fluoxetine in obese female subjects. Obes Res 1995; 3: 345-356.8. Swann AC, Johnson BA, Cloninger CR, Chen YR: Relationships of plasma tryptophan availability to course of illness and clinical features of alcoholism: a preliminary study. Psychopharmacology 143, 380-384, 1999.9. Wurtman RJ, Wurtman JJ: Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res 1995; 3 (Suppl. 4): 477S-480S.10. Cowen PJ, Clifford EM, Williams C, Walsh AES, Fairburn CG: Why is dieting so difficult. Nature 1995; 376: 557.11. Wolfe BE, Metzger ED, Stollar C: The effects of dieting on plasma tryptophan concentration and food intake in healthy women. Physiol Behav 1997; 61 (Suppl. 4): 537-541.12. Wolever TM, Jenkins DJ, Josse RG, Wong GS, Lee R, Anderson GH: Relationship between fasting serum tryptophan/large neutral amino acid ratio and reported hunger in subjects with diabetes. Diabetes Res 1988; 9 (Suppl. 3): 131-137.13. Serra F, Picó C, Johnston J, Carnie J, Palou A. Opposite response to starvation of TRP/LNAA ratio in lean and obese Zucker rats. Biochem Mol Biol Int 1993; 29 (Suppl 3): 483-491.14. Italian Consensus Conference: Overweight, Obesity and Health. Rome, 5 y 6 abril 1991.15. Picó C, Pons A, Palou A: A significant pool of amino acids is adsorbed on blood cell membranes. Biosci Rep 1991; 11: 223-230.16. Arola Ll, Herrera E, Alemany M. A new method of deproteinization of small samples of blood plasma for amino acid determination. Anal Biochem 1977; 82: 236-239.17. Bidlingmeyer BA, Cohen SA, Tarvin TL: Rapid analysis of amino acids using pre-column derivatization. J Chromatogr 1984; 336: 93-104.18. Armstrong MD, Stave U: A study of plasma free amino acid levels. II. Normal values for children and adults. Metabolism 1973a; 22: 561-569.19. Armstrong MD, Stave U. A study of plasma free amino acid levels. III. Variations during growth and aging. Metabolism 1973b; 22: 571-578.20. Björnesjö KB: The distribution of alpha amino nitrogen, urea nitrogen, and non protein nitrogen between erythrocytes and plasma in healthy males and females. Scand J Clin Lab Invest 1963; 15: 25-37.21. Milsom JP, Morgan MY, Sherlock S: Factors affecting plasma amino acid concentrations in control subjects. Metabolism 1979; 28: 313-319.22. 23. Craft IL, Peters TJ: Quantitative changes in plasma amino acids induced by oral contraceptives. Clin Sci 1971; 41: 301-307.24. Proenza AM, Roca P, Virgili J, Remesar X, Alemany M, Palou A: Estrogen effects on blood amino acid compartmentation. Life Sci 1995; 57 (Suppl 17): 1589-1597.25. Björntorp P: Metabolic implications of body fat distribution. Diabetes Care 1991; 14: 1132-1143.26. Krotkiewski M, Björntorp P, Sjöström L, Smith U: Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest 1983; 72: 1150-1162.27. Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman M. F, Julius D: Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 1995; 374: 542-546.28. Fernstrom MH, Fernstrom JD: Brain tryptophan concentrations and serotonin synthesis remain responsive to food consumption after the ingestion of sequential meals. Am J Clin Nutr 1995; 61 (Suppl. 2): 312-319.29. Pijl H., Cohen AF, Verkes RJ, Koppeschaar HPF, Iestra JA, Shoemaker HC, Frölich M, Onkenhout W, Meinders AE: Plasma amino acid ratios related to brain serotonin synthesis in response to food intake in bulimia nervosa. Biol Psychiatry 1995; 38 (Suppl. 10): 659-668.30. Spedding M, Ouvry C, Millan M, Duhault J, Dacquet C: Neural control of dieting. Nature 1996; 380: 488.31. Fluoxetine Bulimia Nervosa Collaborative Study Group. Fluoxetine in the treatment of bulimia nervosa: A multicenter, placebo-controlled, double-blind trial. Arch Gen Psychiatry 1992; 49: 139-147.32. Noach EL: Appetite regulation by serotoninergic mechanisms and effects of d-fenfluramine. Neth J Med 1994; 45 (Suppl. 3): 123-133.
