In rodent models fed HFD, the mitochondrial function of adipocytes is severely impaired (123-126); mitochondrial proteins such as PGC1α are decreased, and there is an increase in ROS and mitochondrial fragmentation via fission, ultimately resulting in mitophagy (123-126) Additionally, mice with an adipose tissue–specific PGC1α deletion, when challenged with a HFD, develop insulin resistance and a reduction in OXPHOS proteins in the WAT, further emphasizing the pivotal role of mitochondria in adipocytes to maintain metabolic homeostasis (127). The gene discussed is PPARGC1A; the disease is Insulin resistance.