LiSDMA · Liver steatosis drives muscle atrophy in type 2 diabetes patients.

Liver steatosis drives muscle atrophy in type 2 diabetes patients.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and encompasses a histological spectrum of liver diseases. It starts with a fatty liver (also called hepatic steatosis) and can progress to more severe stages which include the appearance of inflammation and scarring. A fatty liver is highly prevalent and is found in ~25% of all adults, in up to ~70% of adults who are overweight, and in >90% of the individuals who are morbidly obese, indicating a close link with obesity. It is well known that the liver plays an key role in the regulation of whole-body metabolism, and a fatty liver has been linked to metabolic abnormalities, including insulin resistance, cardiometabolic diseases, and muscle loss. Muscle loss may have serious consequences in individuals as it results in poor physical performance and increased incidence of falls. Furthermore, skeletal muscle acts as a glucose reservoir; thus, individuals who lose muscle mass often enter a vicious cycle that leads to a decreased glucose control, to more muscle loss, and eventually to hospitalization, decreased quality of life, and death. It is therefore important to investigate the role of the fatty liver in the development of muscle loss. The liver exerts many of its effects by 'inter-organ cross-talk'; the liver produces proteins and secretes these into the systemic circulation to affect metabolism elsewhere. In a previous study, I showed for the first time that hepatic steatosis altered the protein secretory profile, and that this altered profile leads to insulin resistance in skeletal muscle. Hence, it was the aim of the current project to determine whether the fatty liver also drives muscle atrophy via inter-organ cross-talk. To investigate our research goal, we fed mice a low or a high fat diet to induce a fatty liver, after which the livers were excised and cut into thin slices. Secretion products from the lean and fatty liver slices were collected and placed on muscle cells to measure muscle protein synthesis and breakdown. Interestingly, protein breakdown was increased in muscle cells incubated with secretion products from the fatty liver slices, while there was no effect on protein synthesis. The results of this study support the hypothesis that secretion products from the fatty liver contribute to the development of muscle atrophy in individuals with NAFLD.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз