Gut-liver axis: An emerging target for exercise in obesity management

Gut dysbiosis emerged as a potential metabolic dysfunction-associated steatotic liver disease (MASLD) trigger due to leaky gut and LPS leakage (endotoxemia). MASLD attracts attention from the scientific community due to the non-existence of a specific treatment, the intimate connection to obesity, and its multiple triggers. In this context, physical exercise is a relevant non-pharmacological strategy. However, different intensities and periodicities can produce divergent results, and their impact on the gut-liver axis remains unraveled. Therefore, this comprehensive review outlines the contribution of exercise (MICT or HIIT) to modulating the gut-liver axis in experimental obesity models, with a focus on the intestinal barrier and hepatic mitochondrial and endoplasmic reticulum (ER) homeostasis. The effects of both exercise protocols are likely related to restoring tight junctions and improving gut permeability. Ceased endotoxemia alleviates MASLD by targeting the endoplasmic reticulum (ER) and mitochondria, countering disturbances caused by glucolipotoxicity and inflammation, like ER stress and mitochondrial dyshomeostasis. Although HIIT is superior to MICT in enhancing gut structure and microbiota diversity and possibly mitigating MASLD due to reduced adiposity and improved insulin sensitivity, regular exercise should be encouraged to counter the obesity pandemic by modulating the gut-liver axis.