Weight regain is a common problem for people who are struggling with weight loss. A number of studies have shown that weight loss in overweight people results in a decrease in whole-body energy expenditure. This decrease in energy expenditure is disproportionate across tissues, known as the energetic mismatch that arises 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 alter skeletal muscle mitochondrial respiration, the mechanisms are not fully understood and there is no direct evidence.
In April 2023, Professor Katsuhiko Funai of the University of Utah published a study in life metabolism Entitled “Weight loss increases skeletal mitochondrial energy efficiency in obese mice” (DOI: 10.1093/lifemeta/load014). Funai and colleagues found that during weight loss in obese mice, the efficiency of oxidative phosphorylation in the mitochondrial skeleton increases, which leads to a decrease in energy expenditure throughout the body, which in turn contributes to regaining lost weight.
Specifically, obese mice were treated with dietary weight loss interventions, followed by a series of high-resolution respirometry and fluorometric measurements. In addition, changes in mitochondrial energy metabolism, mitochondrial proteins, and mitochondrial lipids were examined in weight loss mice. The results showed no significant change in mitochondrial proteins or respiratory super chain formation in the skeletal muscles of weight-losing mice, but the efficiency of oxidative phosphorylation was significantly increased.
Finally, by analyzing skeletal muscle fat in weight-loss mice, the authors found that weight loss accelerates the remodeling of cardiolipin (CL) acyl chains to increase the content of tetralinoleic CL (TLCL), a type of lipid thought to be functional. Critical for respiratory enzymes. Other studies have shown that knocking down CL acyltransferase tafazzin reduces levels of TLCL as well as levels of oxidative phosphorylation of skeletal muscle, allowing mice to avoid diet-induced weight gain. Altogether, the evidence suggests that weight loss results in more efficient mitochondrial energy production in skeletal muscle, thereby reducing energy expenditure throughout the body.
Ferrara, P.J., et al. (2023). Weight loss increases skeletal mitochondrial energy efficiency in obese mice. life metabolism. doi.org/10.1093/lifemeta/load014.