Role of calcitonin gene-related peptide in energy metabolism

Calcitonin gene-related peptide (CGRP) is a neuropeptide produced by alternative tissue-specific splicing of the primary transcript of the CALC genes. CGRP is widely distributed in the central and peripheral nervous system, as well as in several organs and tissues. The presence of CGRP in the liver and brown and white adipose tissue suggests an effect of this neuropeptide on regulation of energy homeostasis. In this review, we summarize the current knowledge of the effect of CGRP on the control of energy metabolism, primarily focusing on food intake, thermoregulation and lipid metabolism in adipose tissue, liver and muscle. CGRP induces anorexia, stimulating anorexigenic neuropeptide and/or inhibiting orexigenic neuropeptide expression, through cAMP/PKA pathway activation. CGRP also induces energy expenditure, increasing the skin temperature and brown adipose tissue thermogenesis. It has been also suggested that information related to peripheral lipid stores may be conveyed to the brain via CGRP-sensory innervation from adipose tissue. More recently, it was demonstrated that mice lacking alpha CGRP are protected from obesity induced by high-fat diet and that CGRP regulates the content of lipid in liver, muscle and adipose tissue. It is unclear the receptor responsible by CGRP effects, as well as whether this neuropeptide acts directly or indirectly in liver, muscle and adipose tissue.