Serum calcitonin gene-related peptide facilitates adipose tissue lipolysis during exercise via PIPLC/IP3 pathways

Calcitonin gene-related peptide (CGRP) is formed by alternative transcription of the calcitonin/α-CGRP gene, which also gives rise to calcitonin (CT). Recently, CGRP has been the focus of research for its metabolic effects in vitro. In the present study, the in vivo effects of CGRP on epididymal fat pads lipolysis at rest and during exercise were investigated in trained male Wistar rats.

Male Wistar rats were assigned to control and trained groups, which underwent endurance training for 12 weeks. The control (at rest) and trained (during acute exercise) animals were subjected to an intravenous injection of rat recombinant CGRP (2 µg kg^-1) and CGRP-(8-37), a competitive CGRP receptors antagonist, to evaluate if and how CGRP can affect adipose tissue lipolysis at rest and during exercise.

Intravenous injection of rat CGRP recombinant at rest upregulated major lipolysis pathways (cyclic AMP (cAMP), AMP-activated protein kinase (AMPK), and phospholipase C (PIPLC/IP₃)) in fat pads, causing an elevation in plasma-free fatty acid (FFA) and a decrease in plasma triglyceride (TG). All the effects were eliminated by pretreating the animals with CGRP-(8-37), suggesting that CGRP receptors were necessary for lipolytic effects of CGRP in fat pads. In trained animals, acute exercise augmented CGRP in serum, cerebrospinal fluid (CSF), and the cortex. Pretreating the animals with CGRP-(8-37) attenuated PIPLC/IP₃ pathway in fat pads and had no effect on cAMP and AMPK pathways.

Epididymal fat pads is a metabolic target for CGRP during exercise and CGRP effects on adipose tissue metabolism during exercise could be related to PIPLC/IP₃ pathway.