Semaglutide remodels visceral adipose tissue lipid metabolism, cutting adipocyte size and inflammation in T2DM mice.

Type 2 diabetes mellitus (T2DM) is a growing public health challenge, often linked to dysfunctional visceral white adipose tissue and altered lipid metabolism. Current treatments for T2DM primarily focus on glycemic control, but a deeper understanding of how therapies impact adipose tissue at a molecular level is crucial. This study aimed to elucidate the specific molecular mechanisms by which semaglutide, a GLP-1R agonist, modulates lipid metabolism and inflammation within visceral adipose tissue in a T2DM model, addressing a key gap in understanding its pleiotropic benefits.

Male C57BL/6J mice were assigned to normal diet, high-fat diet with streptozotocin (HFD+STZ) for T2DM induction, or HFD+STZ with semaglutide treatment. Blood, liver, and epididymal white adipose tissue were collected. Primary endpoints included systemic metabolism (body weight, glucose, insulin resistance), serum adipokines (Leptin, IL-6, TNF-α, Adiponectin), and liver function. Adipose tissue and liver underwent H&E and IHC for F4/80. Targeted lipidomic analysis of epididymal WAT was performed via LC-MS/MS, alongside RT-qPCR for gene expression of adipokines, inflammation, and lipid metabolism.