Histidine induces lipolysis through sympathetic nerve in white adipose tissue.

Abstract

Hypothalamic neuronal histamine has been shown to increase lipolysis in white adipose tissue. The present study aimed to clarify whether peripheral loading with L-histidine, a precursor of neuronal histamine, may affect lipid metabolism in adipose tissue. The in vivo microdialysis study was used to assess lipolysis in rat epididymal adipose tissue by measuring the release of glycerol in response to administration of L-histidine. In addition, electrophysiological measurements were performed to record changes in activity of sympathetic nerve innervating adipose tissue following histidine treatment. Sequential administration of isoproterenol, a beta-adrenoceptor agonist, through the microdialysis cannula at concentrations of 10(-)8 to 10(-6) M increased the glycerol concentration in the dialysate dose-dependently (P < 0.05). Intraperitoneal administration of L-histidine at a dosage of 0.35 mmol kg(-1) also increased the glycerol concentration compared to that of phosphate buffered saline (P < 0.05). Concomitantly, the administration of histidine increased the serum concentration of free fatty acid compared to control treatment (P < 0.05). The accelerating effects of histidine on lipolysis were mimicked by the infusion of 10(2) nmol rat(-1) L-histamine into the third cerebroventricle (P < 0.05). Electrophysiological measurement demonstrated that administration of histidine at a dosage of 0.35 mmol kg(-1) increased the activity of efferent sympathetic nerve, innervating adipose tissue more than the infusion of phosphate buffered saline (P < 0.05). The present results indicate that histidine accelerates lipolysis in white adipose tissue through activation of the sympathetic nerve. The regulation of lipolysis may therefore involve histamine neurons in the brain, probably through the conversion of L-histidine to histamine in the hypothalamus.