Obesity & Energy Demand

Mitochondrial Carrier Homolog 2 (MTCH2) plays a critical role in regulating apoptosis, mitochondrial dynamics, and metabolism. MTCH2’s locus is associated with increased Body Mass Index (BMI) in humans, and its knockout in skeletal muscle protects mice from high-fat diet-induced obesity due to increased whole-body energy utilization.

Here we show, using temporal metabolomics that MTCH2 deletion results in heightened ATP demand, an oxidized environment, elevated lipid/amino acid/carbohydrate metabolism, and a reduction in many metabolites. Lipid-omics reveals that MTCH2 deletion results in a strategic decrease in membrane lipids and an increase in storage lipids. Importantly, the energy imbalance and oxidized environment inhibit adipocyte differentiation, a process requiring energy and a reductive biosynthetic environment. Thus, MTCH2 plays a critical role in maintaining cellular metabolism, energy balance, and redox state, and therefore represents an attractive therapeutic target in metabolic diseases such as obesity.

Chourasia, S…Gross, A. BioRxiv. 2024.