Cellular Reprogramming of Human Primary Adipocytes into Brown Adipose Tissue-Like Cells Preferentially Utilize Glucose

Brown adipose tissue has emerged as a potential therapeutic target for the treatment of 2 diabetes and obesity. This aim of this study is to investigate the role of a disintegrin and metalloprotease 12S expression alone in stimulating cellular reprogramming of a variety of human primary adipocytes into BAT-like cells and if the reprogrammed cells function as brown adipose cells. ADAM 12S-infected cells exhibited significant lipid droplet accumulation, as confirmed by Oil Red O staining and up-regulate PGC-1α, a key regulator of mitochondrial biogenesis, while uncoupling protein-1 resulted in an increased level, but not statistically significant. PR domain-containing 16, a marker of brown fat differentiation, was downregulated in a disintegrin and metalloprotease 12S-infected cells. Metabolic analysis using the Seahorse XF24 platform demonstrated a significant increase in glycolysis and extracellular acidification rates following stress induced by carbonyl cyanide-p-trifluoromethoxyphenylhydrazone and oligomycin compared to basal conditions. Our results suggest human primary adipocytes may be reprogrammed into brown adipose tissue-like cells as possible therapeutic application for type 2 diabetes.