Semaglutide 6-months therapy of type 2 diabetes mellitus restores adipose progenitors potential to develop metabolically active adipocytesстатья
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Дата последнего поиска статьи во внешних источниках: 10 апреля 2024 г.
Аннотация:Background
Nowadays type 2 diabetes mellitus (T2DM) leads to population mortality growth. Today glucagon-like peptide type 1 receptor agonists (GLP-1 RA) are one of the most promising glucose-lowered drugs with anorexigenic and cardioprotective effects. The present study aims to determine the effects of GLP-1 RA semaglutide 6-month therapy on T2DM patient metabolic parameters and adipose progenitor cell health.
Methods
T2DM patients (N = 8) underwent clinical characterization and subcutaneous fat biopsy at start point and after semaglutide 6-month therapy. Adipose-derived stem cells (ADSC) were isolated by enzymatic method. Cell proliferation analysis was performed by MTT and immunocytochemistry. White and beige adipogenesis was analyzed by BODIPY493/503 staining and confocal microscopy. Adipocyte’s metabolic properties were estimated by 3H- and 14C-based metabolic assays. Thermogenesis analysis was performed by ERthermAC staining and confocal microscopy. Protein markers were assessed by Western blotting.
Results
Semaglutide 6-month therapy demonstrated significant anorexigenic and glucose-lowering effects. However, insulin sensitivity (HOMA-IR and M-index) was unchanged after therapy. Semaglutide 6-month therapy increased ADSC proliferation and white and beige adipogenesis. Moreover, lipid droplets fragmentation was observed in beige adipocytes. Both white and beige adipocytes after semaglutide therapy demonstrated 2–3 fold growth of glucose uptake without changes in insulin sensitivity. Newly formed white adipocytes demonstrated glucose utilization for active ATP synthesis, whereas beige adipocytes for canonical thermogenesis.