In parallel, nutrient overload and cytokine stress can impair β-oxidation/oxidative phosphorylation, generate ROS, and disrupt mitochondrial dynamics; MFN2 dysfunction, including the p.Arg707Trp variant, has been associated with symmetric lipomatosis, altered adipokines (elevated FGF-21, decreased leptin/adiponectin), and fragmented mitochondria (7, 16–21). Here, LEP is linked to lipomatosis.