Fructose-palmitate based high calorie induce steatosis in HepG2 cells via mitochondrial dysfunction: An in vitro approach

• Published in: Toxicology in vitro 2020-10, Vol.68, p.104952, Article 104952
• Main Authors: Swapna Sasi, U S, Sindhu, G, Raghu, K.G.
• Format: Article
• Language: English
• Subjects: Aconitate Hydratase - metabolism; Apoptosis; Biochemical analysis; Calcium; Calcium (mitochondrial); Calcium - metabolism; Calcium signalling; Caspase-3; Cytochrome; Cytochrome c; Cytochromes; Depletion; Eating; Electron transport; Electron transport chain; Electron Transport Chain Complex Proteins - metabolism; Energy metabolism; Fatty liver; Fatty Liver - metabolism; Food; Food consumption; Fructose; Fructose - administration & dosage; Hep G2 Cells; Humans; Integrity; Lipids; Lipogenesis; Liver; Liver diseases; Membrane potential; Membrane Potential, Mitochondrial; Mitochondria; Mitochondria - metabolism; Mitochondria - physiology; Non-alcoholic fatty liver disease; Oxidative phosphorylation; Oxygen consumption; Palmitate; Palmitates - administration & dosage; Palmitic acid; Phosphorylation; Proteins; Steatosis; Superoxide; Superoxides - metabolism
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2020.104952

A proper in vitro model for conducting research on high energy food induced steatosis via defective energy metabolism in the liver is not visible in the literature. The present study developed an in vitro model in HepG2 cell line to mimic high energy diet induced steatosis in liver via mitochondrial dysfunction. For this, HepG2 cells were treated with fructose (100 mM) and palmitate (100 μM) for about 24 h and subjected for biochemical analysis relevant to lipogenesis and mitochondrial biology. Our findings showed that fructose-palmitate treatment caused significant lipid accumulation and rise in lipogenic proteins. Further studies showed alteration in mitochondrial integrity, dynamics and oxidative phosphorylation. Mitochondrial integrity was affected by the dissipation of trans-membrane potential, surplus mitochondrial superoxide with calcium overload. Similarly, mitochondrial dynamics were altered with up regulation of mitochondrial fission proteins: DRP1 and FIS1, cytochrome c release, caspase-3 activity and apoptosis. Various components of the electron transport chain: complex I, II, III and IV were altered with significant depletion in oxygen consumption. Overall our findings illustrate the dominant role of mitochondria in the genesis of high fructose-palmitate induced steatosis in HepG2 cells. Since continuous high energy food consumption is the main inducer of steatosis, this model is found to be an ideal one for preliminary and basic research in the area of liver disease via mitochondrial dysfunction. •High fructose and palmitate induce steatosis in HepG2 cells.•Steatosis is mediated by mitochondrial dysfunctions.•Mitochondrial fission was upregulated and while fusion was downregulated during steatosis.•Oxidative phosphorylation and mitobiogenesis was down regulated.•This is an ideal in vitro model for high energy diet induced liver disorder