Metabolic function of the CTRP family of hormones

Abstract

Maintaining proper energy balance in mammals entails intimate crosstalk between various tissues and organs. These inter-organ communications are mediated, to a great extent, by secreted hormones that circulate in blood. Regulation of the complex metabolic networks by secreted hormones (e.g., insulin, glucagon, leptin, adiponectin, FGF21) constitutes an important mechanism governing the integrated control of whole-body metabolism. Disruption of hormone-mediated metabolic circuits frequently results in dysregulated energy metabolism and pathology. As part of an effort to identify novel metabolic hormones, we recently characterized a highly conserved family of 15 secreted proteins, the C1q/TNF-related proteins (CTRP1-15). While related to adiponectin in sequence and structural organization, each CTRP has its own unique tissue expression profile and non-redundant function in regulating sugar and/or fat metabolism. Here, we summarize the current understanding of the physiological functions of CTRPs, emphasizing their metabolic roles. Future studies using gain-of-function and loss-of-function mouse models will provide greater mechanistic insights into the critical role CTRPs play in regulating systemic energy homeostasis.

Figure 1. Schematic of CTRPs

With the exception of CTRP4, every CTRP consists of four domains: a signal peptide for secretion (dark grey), an N-terminal domain with one or more conserved Cys residues (white), a collagen domain with varying numbers of Gly-X–Y repeats (light gray), and a C-terminal globular domain homologous to the immune complement C1q (blue). The numbers on the right refer to the percent amino acid identity between human and mouse orthologs when comparing the full-length protein (first column) or the C-terminal globular domain (second column). CTRP4 and CTRP8 are omitted—the former consists of only two tandem C1q domains, while the latter is absent in the mouse genome.