SIRT3 and obesity due to melanocortin 4 receptor deficiency: However, when exposed to extreme stress such as feeding with high-fat diet (HFD) for 12 months (not 1 week or 3 months), Sirt3−/− mice displayed multiple metabolic syndromes including obesity, insulin resistance, hepatic steatosis, nonalcoholic steatohepatitis, or hyperlipidemias (Hirschey et al., 2011).