Conference proceedings

Serotoninergic mechanisms and obesity

Wurtman R, Wurtman J ...see all

Journal of Nutritional Biochemistry, vol. 9, issue 9 (1998) pp. 511-515

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Brain serotonin appears to be an excellent target for designing drugs to treat obesity. The prototype drug dexfenfluramine accelerates the onset of satiety and suppresses 'carbohydrate craving,' the tendency to consume large quantities of snacks rich in carbohydrates and fats but not proteins. The drug works by blocking serotonin's reuptake into presynaptic terminals; its metabolite norfenfluramine also releases serotonin into synapses and activates certain postsynaptic serotonin receptors. Dopaminergic drugs such as amphetamine and phentermine suppress the appetite but apparently lack macronutrient specificity.The special importance of serotoninergic neurons in feeding behavior derives in part from the fact that eating per se affects the production and release of serotonin. This is because dietary carbohydrates, acting via insulin-which lowers plasma concentrations of the large neutral amino acids (LNAA)-increase the uptake of tryptophan in the brain; this in turn increases the substrate saturation of tryptophan hydroxylase, the key enzyme that converts this amino acid to serotonin. Paradoxically, dietary proteins-which, unlike carbohydrates or fats, do contain tryptophan-decrease tryptophan's uptake in the brain (because they cause disproportionately great increases in blood levels of the other LNAA, which compete with tryptophan for brain uptake), and thus fail to increase brain tryptophan or serotonin levels. Brain serotonin also is critically involved in controling mood, and many patients learn that they can improve their mood by eating carbohydrate-rich, protein-poor foods, particularly as snacks. This carbohydrate craving transiently ameliorates their depressive symptoms, but predisposes to weight gain, a phenomenon readily observed in people with seasonal affective disorder syndrome, premenstrual syndrome, or nicotine withdrawal. Copyright (C) 1998 Elsevier Science Inc.

Author-supplied keywords

  • Carbohydrate craving
  • Carbohydrates
  • Obesity
  • Protein
  • Serotonin
  • Tryptophan

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  • Richard J. Wurtman

  • Judith J. Wurtman

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