Gα_q Is a Heterotrimeric G-Protein Subunit That Directs the Selectivity of PPARγ-Induced Gene Pathways Toward Energy-Related Processes Rather than Adiposity

Authors

• Evelyn A. Bates, University of Kentucky College of MedicineFollow
• Zachary A. Kipp, University of Kentucky College of MedicineFollow
• Wang Hsin Lee, University of Kentucky College of MedicineFollow
• Genesee J. Martinez, University of Kentucky College of MedicineFollow
• Sally N. Pauss, University of Kentucky College of MedicineFollow
• Philipp E. Scherer, University of Texas Southwestern Medical CenterFollow
• Terry D. Hinds, University of KentuckyFollow

Abstract

Background/Objectives: Signaling mediators of PPARγ influence pathways involved in adipogenesis, lipid storage, inflammation, energy-related processes, and glucose utilization. Recent research indicates that PPARγ coregulators, recruited or released during ligand binding, govern specific gene pathways. It was recently discovered that Gα_q, a heterotrimeric G protein subunit, also signals to PPARγ and may significantly affect adipogenesis and glucose sensitivity. Methods: To explore Gα_q’s role in adipocytes, we generated CRISPR-mediated Gα_q (Gnaq) knockout (Gnaq KO) and scramble control cells from 3T3-L1 preadipocytes. Results: The absence of Gα_q resulted in increased lipid accumulation and elevated serine 273 (but not serine 112) phosphorylation of PPARγ. Gα_q deficiency also decreased mitochondrial abundance and respiration in response to PPARγ ligands such as rosiglitazone, pioglitazone, and troglitazone. RNA sequencing comparing differentiated Gnaq KO and control adipocytes identified over 800 differentially expressed genes, including those associated with enhanced lipid metabolism and reduced inflammation. Corresponding PamGene kinome profiling showed increased serine/threonine kinase activity and decreased phosphotyrosine kinase signaling in Gnaq KO adipocytes. Conclusions: These findings support Gα_q as a regulator of adipocyte function, linking kinase signaling pathways to PPARγ-mediated transcription. This research provides mechanistic insights into targeting Gα_q as a potential treatment for individuals with obesity and metabolic disorders.

Document Type

Article

Publication Date

6-1-2026

Notes/Citation Information

Publisher Copyright: © 2026 by the authors.

Digital Object Identifier (DOI)

10.3390/metabo16060418

Archival?

Archival

Repository Citation

Bates, Evelyn A.; Kipp, Zachary A.; Lee, Wang Hsin; Martinez, Genesee J.; Pauss, Sally N.; Scherer, Philipp E.; and Hinds, Terry D., "Gα_q Is a Heterotrimeric G-Protein Subunit That Directs the Selectivity of PPARγ-Induced Gene Pathways Toward Energy-Related Processes Rather than Adiposity" (2026). Markey Cancer Center Faculty Publications. 511.
https://uknowledge.uky.edu/markey_facpub/511