α-Calcitonin gene related peptide (α-CGRP) mediated lipid mobilization in 3T3-L1 adipocytes

• Fibroblasts and 3T3-L1 adipocytes express CGRP-responsive receptors.
• rα-CGRP evokes a biphasic reduction in FFA content in 3T3-L1 adipocytes.
• rα-CGRP regulates FFA content through cAMP independent and cAMP signaling mechanisms.
• FFA and CGRP responses are uncoupled with increasing passage number.
• 3T3-L1 adipocytes have limited utility as a cellular model.

The neuropeptide, α-calcitonin gene-related peptide (α-CGRP), is expressed from sensory nerves that innervate fat. However, how α-CGRP may act in adipose tissue is unclear. Using 3T3-L1 adipocytes we observed that rat α-CGRP (rα-CGRP) evoked either a biphasic or monophasic reduction in intracellular free fatty acid (FFA) content. cAMP production was always monophasic and occurred when FFA responses were absent. Taken together with the observed potencies, these findings suggest that adipose tissue is a physiological target for α-CGRP. However, uncoupling of the FFA and CGRP-signaling responses with increasing passage number limits 3T3-L1 adipocytes as a suitable cellular model.