Is AMP‐activated protein kinase activation a central mechanism of cardio‐metabolic outcomes after metabolic and bariatric surgery?

Metabolic and bariatric surgery (MBS) is the most effective treatment for severe obesity. It usually results in spectacular weight loss, associated with improvements of obesity-associated comorbidities. The mechanisms underlying these benefits are not fully understood but could involve a postoperative activation of the enzyme 5' AMP-activated protein kinase (AMPK). Hence, as AMPK is largely expressed in insulin-sensitive cells, it acts as a key regulator of cardio-metabolic homeostasis, and its activity is down-regulated in tissues from obese, insulin resistant patients. This narrative review aims to summarise the available clinical data regarding changes in AMPK activity following MBS and to discuss the potential relevance of these changes in postoperative physiology. The eight studies reporting specifically changes in AMPK activity following MBS in humans were analysed. They all showed increases in AMPK activity in tissues or blood cells, with effects observed as early as 3 months and persisting beyond 12 months post-surgery. However, the data does not allow us to conclude on (i) the potential specificity of effects depending on the surgery procedure, (ii) the mechanisms involved in the AMPK activation, and (iii) its role in postoperative metabolic outcomes, highlighting that further investigations are warranted to address these issues. Understanding AMPK changes in postoperative physiology could establish its relevance as a potential prognostic marker of surgery metabolic outcomes and as a new target to improve the benefits of MBS. More generally, it may provide insights into the development of novel therapeutic strategies for obesity and associated comorbidities.