Fig. 5: Overview of the roles of Gα12/13 signaling in different metabolic organs.
The roles of Gα12/13 and Gα12/13-coupled receptors, such as G-protein-coupled receptor 40 (GPR40), lysophosphatidic acid receptor (LPA4/6), sphingosine-1-phosphate receptor (S1P3), and the purinergic P2Y6 receptor in metabolic organs, the cardiovascular system, and the immune system, are summarized. Gna12-knockout (KO) mice showed enhanced fasting-induced fat accumulation and diet-induced steatosis in the liver and insulin secretion after high-fat diet (HFD) feeding in the pancreas and promoted an increase in fat mass but decreased fatty acid oxidation in skeletal muscle. Liver-specific Gna13-KO mice developed systemic insulin resistance, whereas skeletal muscle-specific Gna13-KO mice showed myofiber reprogramming and thereby increased whole-body metabolism. T cell-specific Gna12/13-double-knockout (DKO) mice had lymphadenopathy, whereas B cell-specific Gna12/13-DKO mice showed reduced marginal zone B cell (MZB cell) maturation and GC architecture.
