Decision Letter: Human Biallelic MFN2 Mutations Induce Mitochondrial Dysfunction, Upper Body Adipose Hyperplasia, and Suppression of Leptin Expression
January 2017
TLDR MFN2 mutations cause mitochondrial problems, unusual fat distribution, and low leptin despite high body fat.
The study examined the effects of biallelic MFN2 mutations on mitochondrial function and adipose tissue distribution, revealing severe mitochondrial disruption in adipocytes and metabolic abnormalities in patients. Researchers found normal mitochondrial morphology in dermal fibroblasts from three patients but noted elevated blood lactate levels and abnormal mitochondrial protein expression in affected adipose tissues, indicating tissue-selective mitochondrial dysfunction. Significant differences in adipose tissue distribution were observed, with upper body adipose hyperplasia and lower limb lipodystrophy, suggesting differential tolerance to mitochondrial dysfunction. The reviewers recommended further exploration of lipolysis regulation and tissue-specific effects, and the authors agreed to refine their descriptions and consider additional analyses.
