Musculoskeletal And Estrous Cycle Aberrations In A Rodent Model Of Anorexia Nervosa: A Pilot Study

Anorexia nervosa (AN) is a disorder especially common in women and characterized by fear of gaining weight and food restriction, resulting in major hormonal and musculoskeletal alterations. One hormone, estradiol, interacts with muscle to promote muscle size in females; however, no studies have evaluated the possible relationship between AN-induced estradiol alterations and muscle strength. PURPOSE: Evaluate estrous cycle and musculoskeletal alterations in a rodent model of AN. METHODS: Female Sprague Dawley rats (6 weeks of age) underwent ~50% food restriction to mimic caloric restriction of AN (AN, n = 4) or were allowed ab libitum feeding (CON, n = 2) for 20 days. Estrous cycle stage was assessed daily. Grip strength was measured every 5 days during food restriction. Additional assessments of muscle strength were measured before and after food restriction. RESULTS: More time was spent in diestrus/metestrus within 5 days of food restriction (~60% time in diestrus/metestrus in AN vs. ~40% time in diestrus/metestrus in CON). Estrous cycle alterations were even greater after 20 days (~73% time in diestrus/metestrus in AN vs. ~41% in CON). Grip strength differences between AN and CON were noted after 10 days of food restriction (~5% increase from baseline in AN vs. ~27% increase from baseline in CON). After 20 days of food restriction, AN animals had ~20% lower grip strength, ~18% lower muscle area, and ~ 60% lower maximally stimulated dorsiflexion strength compared to CON. Correspondingly, AN animals had ~3-fold greater content of Atrogin and 50% greater MuRF1 mRNA levels in the soleus compared to CON. CONCLUSION: Food restriction results in extensive changes in muscle size and strength in a rodent model. Estrous cycle alterations occur within 5 days of food restriction, and precede muscular declines. These data offer intriguing correlations and support the need for more work to understand the relationship between altered estradiol status and muscular alterations during AN.