Transcriptomic landscape profiling of metformin-treated healthy mice: Implication for potential hypertension risk when prophylactically used

Abstract

Recently, the first-line anti-diabetic drug metformin shows versatile protective effects against several diseases and is potentially prescribed to healthy individual for prophylactic use against ageing or other pathophysiological processes. However, for healthy individuals, it remains unclear what effects metformin treatment will induce on their bodies. A systematic profiling of the molecular landscape of metformin treatment is expected to provide crucial implications for this issue. Here, we delineated the first transcriptomic landscape induced by metformin in 10 tissues (aorta, brown adipose, brain, eye, heart, liver, kidney, skeletal muscle, stomach and testis) of healthy mice by using RNA-sequencing technique. A comprehensive computational analysis was performed. The overrepresentation of cardiovascular disease-related gene sets, positive correlation with hypertension-related transcriptomic signatures and the associations of drugs with hypertensive side effect together indicate that although metformin does exert various beneficial effects, it would also increase the risk of hypertension in healthy mice. This prediction was experimentally validated by an independent animal experiments. Together, this study provided important resource necessary for investigating metformin's beneficial/deleterious effects on various healthy tissues, when it is potentially prescribed to healthy individual for prophylactic use.