Adipocyte G<sub>i</sub> signaling is essential for maintaining whole-body glucose homeostasis and insulin sensitivity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32532984.
- Also identified by DOI 10.1038/s41467-020-16756-x and PMC identifier 7293267.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Adipocyte dysfunction links obesity to insulin resistance and type 2 diabetes. Adipocyte function is regulated by receptor-mediated activation of heterotrimeric G proteins. Little is known about the potential in vivo metabolic roles of G<sub>i</sub>-type G proteins expressed by adipocytes, primarily due to the lack of suitable animal models. To address this question, we generated mice lacking functional G<sub>i</sub> proteins selectively in adipocytes. Here we report that these mutant mice displayed significantly impaired glucose tolerance and reduced insulin sensitivity when maintained on an obesogenic diet. In contrast, using a chemogenetic strategy, we demonstrated that activation of G<sub>i</sub> signaling selectively in adipocytes greatly improved glucose homeostasis and insulin signaling. We also elucidated the cellular mechanisms underlying the observed metabolic phenotypes. Our data support the concept that adipocyte G<sub>i</sub> signaling is essential for maintaining euglycemia. Drug-mediated activation of adipocyte G<sub>i</sub> signaling may prove beneficial for restoring proper glucose homeostasis in type 2 diabetes.
Medical subject headings
- Adipocytes
- GTP-Binding Protein alpha Subunits, Gi-Go
- Insulin Resistance
- Signal Transduction