20-30% of the population in the Western world suffer from non-alcoholic fatty liver disease (NAFLD)1 – a number which is likely to increase dramatically over the next decade as more and more people become obese. NAFLD is associated with several co-morbidities such as type 2 diabetes, cardiovascular disease, and hepatocellular carcinoma and is now the leading cause of obesity-related cancer deaths in middle-aged men in the US2.
New research from Steno Diabetes Center performed in collaboration with Tel Aviv University, University of Maryland, USA, Institute of Clinical Physiology, CNR Pisa, Italy, and University of Helsinki shows that high liver fat decreases the ability of the liver to regulate metabolism3 e.g. when eating. The results have just been published in the scientific journal Nature Communications.
“Despite its importance, non-alcoholic fatty liver disease is poorly understood. Through a complicated procedure that includes catheter implants in the liver, liver biopsies, and comprehensive molecular profiling combined with sophisticated computational modelling of liver metabolism, we have mapped the metabolic processes in the fatty liver”, says principal investigator in the study, Professor Matej Orešič from Steno Diabetes Center.
“What we found is that the liver of non-diabetic persons with NAFLD maintains glycemic control by producing glucose from lipids i.e. triglycerides while decreasing glucose production from lactate. As more fat is stored in the liver this balance eventually breaks down and the liver will start to produce glucose from lactate which markedly increases glucose production. This switch may explain how type 2 diabetes develops in people with non-alcoholic fatty liver disease”.
The process has implications for the liver’s overall ability to adapt and maintain basic metabolic functions such as detoxication or synthesis e.g. carbohydrates or proteins.
“Our findings might help us to first of all identify risk markers of serious comorbidities in persons with NAFLD and secondly to prevent them from occurring”, says Matej Orešič.
- World J Hepatol. 2015 Jun 18; 7(11): 1450–1459.
- Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):656-65
- T. Hyötyläinen, L. Jerby, E. M. Petäjä, I. Mattila, S. Jäntti, P. Auvinen, A. Gastaldelli, H. Yki-Järvinen, E. Ruppin, M. Orešič. Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease. Nat Comm 7, 8994 (2016). doi: 10.1038/ncomms9994