G alpha(12/13) signaling in metabolic diseases

Abstract

As the key governors of diverse physiological processes, G protein-coupled receptors (GPCRs) have drawn attention as primary targets for several diseases, including diabetes and cardiovascular disease. Heterotrimeric G proteins converge signals from similar to 800 members of the GPCR family. Among the members of the G protein alpha family, the G alpha(12) family members comprising G alpha(12) and G alpha(13) have been referred to asgeponcogenes. G alpha(12/13)levels are altered in metabolic organs, including the liver and muscles, in metabolic diseases. The roles of G alpha(12/13) in metabolic diseases have been investigated. In this review, we highlight findings demonstrating G alpha(12/13) amplifying or dampening regulators of phenotype changes. We discuss the molecular basis of G protein biology in the context of posttranslational modifications to heterotrimeric G proteins and the cell signaling axis. We also highlight findings providing insights into the organ-specific, metabolic and pathological roles of G proteins in changes associated with specific cells, energy homeostasis, glucose metabolism, liver fibrosis and the immune and cardiovascular systems. This review summarizes the currently available knowledge on the importance of G alpha(12/13) in the physiology and pathogenesis of metabolic diseases, which is presented according to the basic understanding of their metabolic actions and underlying cellular and molecular bases.