Excessive Fat Burning Induces “Stress” in the Liver and Can Cause Fatty Liver Inflammation

Scientists from Düsseldorf have shown that excessive fat burning causes a stress response in the liver, which explains the connection between obesity, insulin resistance and fatty liver disease. These findings provide new approaches for the prevention and treatment of fatty liver disease.

Fatty liver is the most common pathological liver condition in the Western industrial nations. Increasingly, the causes are to be found less in excessive alcohol consumption but rather in obesity and type 2 diabetes. These non-alcoholic fatty liver diseases (NAFLD) now constitute the most common cause of liver cirrhosis and liver cancer in the U.S.
In this study for the first time, the researchers directly investigated the role of the mitochondria, the cell’s power stations, in the liver of healthy controls and patients. Scientists of the German Diabetes Center (DDZ), which is also a partner in the German Center for Diabetes Research (DZD), in collaboration with scientists of University Hospital Düsseldorf and St. Martinus Hospital, have now discovered that obese patients with NAFLD have significantly increased mitochondrial activity in the liver. With the further progression to fatty liver inflammation (NASH), the activity of the mitochondria decreases, while oxidative stress increases. “In the early stages of overweight/obesity the liver first increasingly burns excess fat, but it thus becomes overburdened, and the disease can progress. These insights will lead to new approaches for the prevention and treatment of non-alcoholic fatty liver diseases,” said Professor Roden, director of the University Clinic for Endocrinology and Diabetology and board member of the DDZ. The results were published in the prestigious scientific journal Cell Metabolism.

Mitochondria and non-alcoholic fatty liver disease (NAFLD)
Mitochondria regulate the burning of nutrients in the cell to generate energy. NAFLD not only includes fatty liver and NASH, in which the liver contains more than 5 percent fat, but also non-alcoholic liver cirrhosis and liver cancer. Because initially there are only minimal symptoms, NAFLD is often only detected by coincidence or at a late stage. Weight reduction helps only in the early stages; for NASH, however, there is no established therapy.

Original publication:
Koliaki C, Szendroedi J, Kaul K, Jelenik T, Nowotny P, Jankowiak F, Herder C, Carstensen M, Krausch M, Knoefel WT, Schlensak M, Roden M: Adaptation of Hepatic Mitochondrial Function in Humans with Non-Alcoholic Fatty Liver Is Lost in Steatohepatitis; Cell Metabolism, Volume 21, Issue 5, 2015, Pages 739-746