Discovery of peptides as key regulators of metabolic and cardiovascular crosstalk

Abstract

Peptides are fundamental regulators of metabolism, with several already developed as drugs, including glucagon-like peptide-1-based peptide therapeutics for diabetes and obesity. Despite their established importance, our understanding of their biosynthesis, modifications, receptor interactions, and signaling pathways remains incomplete. Advances in peptidomics and proteomics, particularly mass spectrometry, have facilitated peptide discovery and characterization, revealing novel roles for known peptides and uncovering previously unrecognized post-translational modifications. With the increasing prevalence of metabolic diseases driven by obesity, understanding the regulatory functions of peptide hormones has significant therapeutic potential. This review discusses the latest insights into peptide biology, highlighting key examples of peptides controlling tissue crosstalk, as well as how multi-omics technologies, computational approaches, and AI-driven methods are likely to expand our knowledge of peptide-mediated metabolic regulation.

Keywords: CP: Metabolism; crosstalk; metabolism; peptides.

Figure 1.. The physiological and pharmacological effects of Apelin and its receptor and signaling mechanisms

(A) Apelin-13 exerts diverse effects across multiple organs. (B) Schematic representation of Apelin receptor (APJ) signaling through Apelin-13 and Apelin-36. The right image shows a molecular model of the Apelin receptor bound to Apelin-13, with associated G protein subunits, highlighting the receptor’s structure and interaction with signaling components.

Figure 2.. Processing and physiological effects of proghrelin-derived peptide obestatin

(Top) Proghrelin undergoes posttranslational processing in X/A-like cells to produce ghrelin and obestatin. (Bottom) Obestatin has various effects on multiple organs, including regulation of gastrointestinal (GI) motility and feeding behavior.