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Disturbances in the endoplasmic reticulum can be triggered by increased oxidative stress, deposition of saturated fatty acids, hypoxia, or other stimuli, which in turn cause the accumulation of unfolded proteins in the endoplasmic reticulum lumen that is filled with proteins, antioxidants, or essential metals

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SIRT3 expression is downregulated in obese patients, and deletion of SIRT3 leads to increased mitochondrial oxidative stress, reduced energy expenditure and worsened glucose metabolism, resulting in accelerated obesity under a high-fat diet (HFD) feeding [25, 26]