The metabolic role of spermidine in obesity: evidence from cells to community

Spermidine is a natural polyamine existing in all living cells known to play an important role in cellular functions. Recently, several studies have reported the effect of alterations in the spermidine pool on metabolic pathways. It has been shown that activation of spermidine/spermine N-1-acetyl-transferase (SSAT), the rate-limiting enzyme in polyamine catabolism, improved glucose and lipid metabolism. In addition, spermidine supplementation has been shown to protect against diet-induced obesity in animal models. However, some clinical studies demonstrated that polyamine levels are increased in childhood obesity and metabolic syndrome patients with type 2 diabetes (T2DM), while polyamine-rich food is associated with a lower incidence of cardiovascular disease (CVD). Therefore, this review aims to summarize and discuss the evidence from in vitro, in vivo and clinical studies on the possible roles of spermidine on metabolic pathways under physiological and obese conditions. All consistent and inconsistent findings are discussed and further studies aiming to fill any gaps in the knowledge are proposed.