![oxygen not included download 126575 oxygen not included download 126575](https://miro.medium.com/max/942/1*mNDjPDtgB2NM2YVrlRNMUA.png)
Likewise, SIRT3 protects mitochondrial function by modulating ROS generation through several substrates, including superoxide dismutase 2 (SOD2), and the transcription factor Forkhead Box O3A (FOXO3A). Thus, previous studies have reported that SIRT3 controls mitochondrial ATP production through its effects on the respiratory chain. By deacetylating lysine residues, SIRT3 regulates the activity of many proteins to modulate mitochondrial biogenesis, energy generation and reactive oxygen species (ROS) homeostasis. Mitochondrial sirtuin 3 (SIRT3) is a NAD +-dependent protein deacetylase that maintains cellular homeostasis.
![oxygen not included download 126575 oxygen not included download 126575](https://i.imgur.com/O28NUrd.png)
These findings demonstrate new mechanisms by which Sirt3 deficiency contributes to hepatic steatosis. The upregulation in CD36 was confirmed in Huh-7 cells treated with a SIRT3 inhibitor or transfected with SIRT3 siRNA and incubated with palmitate, an effect that was prevented by the Nrf2 inhibitor M元85. Finally, Sirt3 −/− mice fed the HFD showed increased levels of some proteins involved in lipid uptake, such as CD36 and the VLDL receptor.
![oxygen not included download 126575 oxygen not included download 126575](https://thepcgames.net/wp-content/uploads/2017/07/Oxygen-Not-Included-PC-Game-Free-Download4-min.jpg)
These changes were prevented by lipid exposure through a mechanism that might involve a decrease in succinate levels. Interestingly, Sirt3 deficiency in liver and its knockdown in Huh-7 cells resulted in upregulation of the nuclear levels of LIPIN1, a PPARα co-activator, and of the protein that controls its levels and localization, hypoxia-inducible factor 1α (HIF-1α). Sirt3 −/− mice fed a HFD presented exacerbated hepatic steatosis that was accompanied by decreased expression and DNA-binding activity of peroxisome proliferator-activated receptor (PPAR) α and of several of its target genes involved in fatty acid oxidation, compared to WT mice fed the HFD. Studies were conducted in wild-type (WT) and Sirt3 −/− mice fed a standard diet or a HFD and in SIRT3-knockdown human Huh-7 hepatoma cells. In this study, we investigated additional mechanisms that might play a role in aggravating hepatic steatosis in Sirt3-deficient mice fed a high-fat diet (HFD). Deficiency of mitochondrial sirtuin 3 (SIRT3), a NAD +-dependent protein deacetylase that maintains redox status and lipid homeostasis, contributes to hepatic steatosis.