Lactate entrance into the brain facilities adipose tissue lipolysis during exercise via circulating calcitonin gene-related peptide.

Objectives: We assessed the relationships between CGRP, lactate and fat regulation.

Methods: We evaluated the effect of intracerebroventricular (i.c.v.) injection of lactate and acute exercise on brain CGRP expression, and its concentration in serum/cerebrospinal fluid (SCF) in rats.

Results: Injection of lactate up-regulated CGRP expression in the cortex and CSF and activated p38-mitogen-activated protein kinases (p38-MAPK) pathway. Co-injection of lactate and sb203580, deterred lactate-induced up-regulation of CGRP in the brain and CSF. Exercise increased the CGRP expression in the brain and CSF and up-regulated fat metabolism. Inhibition of lactate entrance into the brain using alpha-cyano-4-hydroxycinnamate (4-CIN) diminished exercise-induced CGRP up-regulation in the brain and CSF. Reducing the circulating blood lactate by pre-treatment of the animals with dichloroacetate (DCA) had no effect on exercise-induced increase in CGRP expression or fat metabolism during exercise.

Conclusions: Lactate probably acts as one of a signalling molecule in the brain to regulate fat metabolism during exercise.