Hormonal
Genetic deletion or specific knockdown of the mitochondrial protein MCJ (DnaJC15) in brown adipose tissue promotes thermogenesis and protects against diet-induced obesity through a UCP1-independent mechanism mediated by eIF2α signaling.
This research suggests that targeting the MCJ protein in fat cells could help the body burn more energy and resist weight gain, even without relying on the classic 'uncoupling' protein UCP1. While this is currently a genetic finding in mice, it points to potential future therapies for obesity that enhance metabolic rate through mitochondrial stress responses.
MCJKO mice, even without UCP1, a fundamental thermogenic protein, exhibit elevated BAT thermogenesis... The pivotal role of eIF2α is scrutinized by in vivo CRISPR deletion of eIF2α in MCJKO mice, abrogating thermogenesis.
Why this rating
Strong mechanistic evidence using multiple mouse models (global KO, BAT-specific KO, UCP1 cross-KO) and human data, though translated to clinical obesity therapy.
Source
Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis
Beatriz Cicuéndez et al. · Nature Communications · 2025
DOI 10.1038/s41467-024-54353-4
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