Mitochondrial adaptation in steatotic mice

• Published in: Mitochondrion Vol. 40; pp. 1 - 12
• Main Authors: Einer, Claudia, Hohenester, Simon, Wimmer, Ralf, Wottke, Lena, Artmann, Renate, Schulz, Sabine, Gosmann, Christian, Simmons, Alisha, Leitzinger, Christin, Eberhagen, Carola, Borchard, Sabine, Schmitt, Sabine, Hauck, Stefanie M, von Toerne, Christine, Jastroch, Martin, Walheim, Ellen, Rust, Christian, Gerbes, Alexander L, Popper, Bastian, Mayr, Doris, Schnurr, Max, Vollmar, Angelika M, Denk, Gerald, Zischka, Hans
• Format: Journal Article
• Language: English
• Published: Netherlands 01.05.2018
• Subjects: Adaptation, Physiological; Adenosine Triphosphate - metabolism; Animals; Calcium - metabolism; Diet - methods; Disease Models, Animal; Fatty Acids - administration & dosage; Fatty Liver - pathology; Hepatocytes - pathology; Lipid Metabolism; Mice; Mitochondria - metabolism; Mitochondria - physiology; Mitochondria; NAFLD; Steatosis; Western diet
• ISSN: 1567-7249; 1872-8278
• DOI: 10.1016/j.mito.2017.08.015

Western lifestyle-associated malnutrition causes steatosis that may progress to liver inflammation and mitochondrial dysfunction has been suggested as a key factor in promoting this disease. Here we have molecularly, biochemically and biophysically analyzed mitochondria from steatotic wild type and immune-compromised mice fed a Western diet (WD) - enriched in saturated fatty acids (SFAs). WD-mitochondria demonstrated lipidomic changes, a decreased mitochondrial ATP production capacity and a significant sensitivity to calcium. These changes preceded hepatocyte damage and were not associated with enhanced ROS production. Thus, WD-mitochondria do not promote steatohepatitis per se, but demonstrate bioenergetic deficits and increased sensitivity to stress signals.