Mitochondrial capacities and quality control following short‐ and long‐term weight restoration after simulated anorexia nervosa

Anorexia nervosa (AN) is a psychiatric disorder characterized by prolonged caloric restriction and skeletal muscle atrophy. Mitochondrial health is a key mediator of muscle function, yet the role of mitochondria during AN and following weight regain has not been investigated. The objective of this study was to evaluate mitochondrial capacities and quality control mechanisms in a rodent model of AN, spanning the acute underweight phase and multiple recovery periods. Through a series of experiments, 8-week-old female Sprague-Dawley rats underwent a 30-day simulated AN protocol, followed by different durations of weight recovery via ad libitum feeding. Following designated interventions, muscle performance on a submaximal fatiguing protocol and components of mitochondrial function were evaluated. AN resulted in 23%-25% lower muscle performance compared to healthy controls, and these alterations remained even after short-term weight gain. AN rats had 23% lower contribution of complex I to maximal mitochondrial electron transfer as well as alterations to genes important for mitochondrial translation and dynamics, many of which were not resolved with short-term recovery. With long-term recovery, muscle performance and mRNA content of genes related to mitochondrial translation were similar to healthy controls. However, genes related to mitochondrial fission were greater than healthy controls. AN results in reduced muscle performance during a fatiguing protocol, reliance on mitochondrial complex I and genes related to mitochondrial quality control. Many alterations persist with short-term weight recovery; however, given sufficient time, many facets of mitochondrial health appear to normalize following AN, though there still may be long-term consequences to mitochondrial dynamics.