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Widespread disease: inflammation and insulin resistance threaten fatty liver


Special liver fats are a warning sign of fatty liver inflammation and insulin resistance

Liver disease usually develops a long time before the first physical symptoms appear. This also applies to the so-called non-alcoholic fatty liver diseases, which can develop into a so-called fatty liver inflammation and are often associated with an increased risk of diabetes.

A research team from the German Diabetes Center and the Touchstone Diabetes Center in Texas (USA) has now found that certain biologically active substances that can be measured in liver samples indicate the risk of insulin resistance and inflammation of the liver. This also opens up new approaches to explaining the connection between non-alcoholic fatty liver diseases and the development of diabetes. The researchers have published their results in the journal "Diabetes Care".

Link between diabetes and fatty liver disease

According to the researchers, around 50 to 75 percent of people with type 2 diabetes worldwide have fatty liver. In addition, ten to 20 percent of the patients showed so-called fatty liver inflammation (steatohepatitis), liver cirrhosis or even a liver carcinoma resulting from this (liver cancer). In their current study, the scientists now investigated the question of whether "specific fat breakdown products in the liver (sphingolipids) can contribute to the development of insulin resistance, oxidative stress and inflammatory processes and can indicate an upcoming diabetes disease," according to the German Diabetes Center.

Different groups examined

For their investigations, the researchers analyzed the liver samples from healthy, slim people and people with pathological obesity, who underwent bariatric surgery (surgery to remedy pathological obesity). The 21 participating overweight patients were further divided into three groups based on the status of the fatty liver disease. The first group had no fatty liver, the second group had an early stage fatty liver with no signs of inflammation and the third group had advanced inflammation with increased connective tissue formation in the liver.

Biomarkers for insulin sensitivity and oxidative stress

The researchers found that people with insulin resistance and fatty liver inflammation had elevated levels of several so-called sphingolipids. Some of these lipids are biomarkers of insulin sensitivity, oxidative stress and inflammatory processes in the liver, which suggests that these products of fat metabolism contribute to the progression of simple fatty liver to non-alcoholic fatty liver inflammation (NASH), emphasizes study leader Prof. Dr. Michael Roden. The researchers identified the various forms of fatty liver disease on the basis of a liver biopsy. In the liver samples and also in other tissues such as muscles and various adipose tissues, so-called ceramides were determined, which belong to the sphingolipids that form important components of the cell membrane as biologically active substances, the researchers explain.

So-called ceramides with a decisive influence

Obesity and type 2 diabetes have long been associated with non-alcoholic fatty liver disease (NASH). The results now available show that the ceramides may play a role here. For example, the group of patients with non-alcoholic fatty liver disease had a higher concentration of total ceramides in the liver compared to the other groups, and in addition, specific ceramides were only characteristically increased in this group of patients, reports the German Diabetes Center.

Further investigations are to follow

The scientists report that ceramides, which are specifically increased in NASH patients, are associated with pronounced inflammation and oxidative stress, decreased function of the mitochondria (cell power plants) in the liver and pronounced insulin resistance. "The higher the value of certain ceramides, the worse the insulin sensitivity became," the experts continued. Additional analyzes of various subgroups of sphingolipids are now required, which may possibly also explain processes in the cells during the development of NASH and type 2 diabetes. (fp)

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