Roden 2023 MiP2023
Link: MiP2023 Obergurgl AT
Roden Michael (2023)
Event: MiP2023 Obergurgl AT
Introduction: Common metabolic diseases such obesity and type 2 diabetes associate with insulin resistance (1), but also with impaired mitochondrial function in several tissues such as skeletal muscle and adipose tissue (2,3). Assessment of hepatic mitochondrial functionality in the liver is more challenging because of invasive and complex methodology, which limits large-scale studies in human.
Results and Discussion: Previously, employing noninvasive multitracer magnetic resonance spectroscopy we found reduction in hepatic ATP concentration and synthesis in humans with type 2 diabetes, but not in those with obesity (4). Subsequent high-resolution respirometry studies allowed us to detect an adaptation of hepatic oxidative capacity to excessive lipid availability (mitochondrial plasticity) in humans with obesity, which is lost with progressive non-alcoholic fatty liver disease, i. e. steatohepatitis (NASH) (5). The loss of mitochondrial plasticity goes along impaired antioxidant defense leading to increased H202 production and lipid peroxidation. These alterations are even more pronounced in people with type 2 diabetes or with increasing liver fibrosis (6). The alterations of mitochondrial function are preceded by changes in mitochondrial quality control and help to explain ultrastructural features of NASH such megamitochondria. Adipose tissue dysfunction (1), specifically impairment of insulin sensitivity and mitochondrial oxidative capacity in visceral adipose tissue (7), could be the initial driving force of altered hepatic energy metabolic and common metabolic diseases.
- Roden M, Shulman GI (2019) The integrative biology of type 2 diabetes. doi: 10.1038/s41586-019-1797-8. Epub 2019 Dec 4.
- Fromenty B, Roden M. Mitochondrial alterations in fatty liver diseases. J Hepatol. 2023 Feb;78(2):415-429. https://doi.org/10.1016/j.jhep.2022.09.020. Epub 2022 Oct 7.
- Targher G, Corey KE, Byrne CD, Roden M (2021) The complex link between NAFLD and type 2 diabetes mellitus - mechanisms and treatments. https://doi.org/10.1038/s41575-021-00448-y. Epub 2021 May 10.
- Szendroedi J, Chmelik M, Schmid AI, Nowotny P, Brehm A, Krssak M, Moser E, Roden M (2009) Abnormal hepatic energy homeostasis in type 2 diabetes. https://doi.org/10.1002/hep.23093.
- Koliaki C, Szendroedi J, Kaul K, Jelenik T, Nowotny P, Jankowiak F, Herder C, Carstensen M, Krausch M, Knoefel WT, Schlensak M, Roden M (2015). Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. https://doi.org/10.1016/j.cmet.2015.04.004.
- Pafili K, et al. (2022) Mitochondrial respiration is decreased in visceral but not subcutaneous adipose tissue in obese individuals with fatty liver disease. https://doi.org/10.1016/j.jhep.2022.08.010. Epub 2022 Aug 19.
- Gancheva S, et al. (2022) Impaired Hepatic mitochondrial capacity in nonalcoholic steatohepatitis associated with type 2 diabetes. https://doi.org/10.2337/dc21-1758.
• O2k-Network Lab: DE Duesseldorf Roden M
Labels: Pathology: Diabetes, Obesity
Organism: Human Tissue;cell: Liver, Fat