The pro-obesity role of G3BP1 through altering adipogenic differentiation in mice via the PI3K/AKT pathway

As a growing but non-infectious epidemic, obesity is a common cause of several comorbidities. GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is a central regulator of stress‑granule assembly that has significant implications in metabolic disorders. This article aims to explore the functional mechanism of G3BP1 in obesity, both in vitro and in vivo. Functional assays were used to detect cellular phenotypes. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were also used to test metastasis-, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling- and Wnt/β-catenin signalling-related genes. Oil‑red‑O staining and haematoxylin and eosin (H&E) staining were used to estimate lipid deposition. RT-qPCR, western blotting, and immunofluorescence staining were used to determine adipocyte differentiation and lipid metabolism. The TOPFlash/FOPFlash reporter assay was used to identify β-catenin activity. In a murine model fed a high-fat diet (HFD, 60% fat), body weight was measured prior to the detection of adipokine levels by enzyme‑linked immunosorbent assay (ELISA), triacylglycerol (TG) concentration using an assay kit, and adipogenic marker genes by western blotting. G3BP1 knockdown inhibited proliferation, migration, invasion, and adipogenesis, and induced cell cycle arrest in 3T3-L1 preadipocytes, and decreased body weight and adipogenesis and fat accumulation in obese mice. G3BP1 activated Wnt/β-catenin and PI3K/AKT pathways. LY294002 (PI3K inhibitor) and SC3036 (PI3K activator) reversed the in vitro effects of G3BP1 or silenced G3BP1 on preadipocyte invasion. G3BP1 may promote preadipocyte proliferation, migration, invasion, and adipogenesis to promote the progression of obesity, which might be relevant to the PI3K/AKT pathway.