Obesity is a chronic disease, defined as the accumulation of abnormal or excessive fat in adipose tissue, and a risk factor for several non-communicable diseases. There is a great health and economic impact associated with obesity, mainly due to increased comorbidities. Although not all patients with obesity develop a chronic liver disease, the metabolic-associated fatty liver disease (MAFLD) often coexists with obesity, which contributes to liver fibrosis, a known risk factor for the development of hepatocellular carcinoma (HCC).

Bariatric metabolic surgery (BMS) is currently one of the most effective interventions for obesity and associated conditions, when compared with intensive medical and lifestyle interventions. Regarding liver function, there is evidence for improvements of steatosis, inflammation, fibrosis and transaminases levels in most patients, and decreased risk for HCC after BMS. Nevertheless, others reported persistent liver fibrosis, increased risk of alcoholic cirrhosis or even hepatic function impairment after BMS.

Importantly, sarcopenia (defined as the loss of skeletal muscle mass and strength along with a decrease in physical performance) is commonly linked with chronic liver diseases in a complex relationship involving hepatokines and myokines, associated with increased risk of steatohepatitis and hepatic fibrosis. This means that loss of muscle mass and strength may contribute to the deterioration of liver diseases.

So, we hypothesize that the function of the skeletal muscle is an important biological driver of the failure to fully benefit from BMS for the liver improvement associated with the weight loss. We anticipate that changes in skeletal muscle gene expression and in the secretion of muscle-derived circulating factors may be involved in this response, which may partially explain the inter-individual variability observed in the response to BMS of patients with obesity.
EMPhaSize project is at the forefront of integrating molecular biology with clinical practice in managing obesity. Its methodology not only promises advancements in understanding resistance to the surgical treatment of obesity in terms of liver improvements, but also paves the way for the discovery of novel therapeutic solutions for metabolic diseases. Our advanced computational approach will be aligned with the complexity and interconnectivity of the obtained data, by creating a matrix, performing metadata curation and organization, allowing the generation of biomodels in machine-readable file format, ultimately transformed in real-world clinical tools.

Paçavras chave - obesity; skeletal muscle; liver; computational analysis