Thermogenic actions of tryptophan in the rat are mediated independently of 5-HT

Abstract

Serotonin (5-HT) has been implicated in the central control of energy balance, via inhibition of food intake and stimulation of thermogenesis. Its rate of synthesis in brain is dependent on the availability of its precursor amino acid, tryptophan. The objective of the present study was therefore to investigate the thermogenic actions of tryptophan and to determine whether these actions are mediated by 5-HT. Central or peripheral injections of 5-HT (i.c.v.; 0.5–40μg), 5-hydroxytryptophan (5-HTP) (i.c.v.; 20μg) or tryptophan (i.p.; 20 mg/kg, i.c.v.; 12–60 μg) significantly increased resting oxygen consumption (uc|dot|V O2 by approximately 15–20%) in conscious rats, without apparent effects on physical activity. Small increases (5–7%) in uc|dot|V O2 were also observed following peripheral injections of aspartate or glycine (20 mg/kg) but not taurine, whilst central injection of tyrosine or leucine (15–18 μg) significantly increased uc|dot|V o2 by 15%. We have previously reported that the thermogenic and anorexic actions of 5-HT are mediated by corticotropin-releasing factor (CRF) 16. In the present study, the thermogenic actions of 5-HTP, like those of 5-HT, were significantly reduced by pretreatment (5 min before) with the CRF antagonist α-helical CRF 9–41 (25 μg, i.c.v.) or a polyclonal antibody to CRF. However, the thermogenic actions of tryptophan were not significantly modified by pretreatment with either the 5-HT antagonist, methylsergide (20 μg, i.c.v.) or with the CRF antagonist or antibody and thus appear to act through different mechanisms to 5-HT. Despite the well-documented effects of tryptophan on serotonergic systems, tryptophan administration (i.c.v.) did not significantly affect the concentration of either 5-HTP, 5-HT or its metabolite 5-HIAA within the cerebrospinal fluid or in the whole hypothalamus, measured 1 h post-injection. Similarly, no changes in the concentrations of other amino acids were observed either in the plasma or whole hypothalamus. In summary, central thermogenic actions of tryptophan are described which appear to be independent of 5-HT.