Weight loss leads to increased efficiency of skeletal muscle mitochondrial energy production [Beuzz]

Weight regain is a common problem for people who lose weight. A number of studies have shown that weight loss in overweight people leads to a reduction in whole-body energy expenditure. This reduction in energy expenditure is disproportionate across tissues, known as energy mismatch which comes primarily from lean tissue, thus increasing the risk of weight regain. Although this phenomenon has long been identified and it has been suggested that weight loss may impair mitochondrial respiration in skeletal muscle, the mechanisms are not fully understood and direct evidence is lacking.

In April 2023, Professor Katsuhiko Funai from the University of Utah published a study in life metabolism entitled “Weight loss increases mitochondrial energy efficiency of skeletal muscle in obese mice” (DOI: 10.1093/lifemeta/load014). Funai and colleagues found that during weight loss in obese mice, the efficiency of mitochondrial oxidative phosphorylation of skeletal muscle increased, leading to reduced energy expenditure throughout the body, which in turn contributes to rebound of weight loss.

Specifically, obese mice were treated with dietary interventions to lose weight, followed by a combination of respirometry and high-resolution fluorometry measurements. Additionally, changes in mitochondrial energy metabolism, mitochondrial proteomes, and mitochondrial lipidomes were examined in weight-loss mice. The results showed that there was no significant change in mitochondrial proteomes or respiratory chain supercomplex formation in skeletal muscle of the slimming mice, but the efficiency of oxidative phosphorylation was significantly increased.

Finally, by analyzing the skeletal muscle lipidome in weight loss mice, the authors found that weight loss accelerated the remodeling of mitochondrial cardiolipin (CL) acyl chains to increase the content of tetralinoleoyl CL (TLCL), a species of lipids that were thought to be functionally critical for respiratory enzymes. Other studies showed that removal of tafazzine CL acyltransferase reduced TLCL levels as well as skeletal muscle oxidative phosphorylation levels, allowing mice to avoid diet-induced weight gain. Overall, the evidence suggests that weight loss leads to an increase in the efficiency of skeletal muscle mitochondrial energy production, thereby reducing energy expenditure throughout the body.