Dietary Composition Exacerbates Sex Differences in Skeletal Muscle Myopathy following Chronic Alcohol Intake
Authors: Laudato Joseph A. , Tice Abby L. , Dunlap Kirsten R. , Keith Zachary A. , Steiner Jennifer L. 
Published: April 2020

Chronic alcohol consumption has been commonly reported to induce skeletal muscle loss, however data observing the impact of diet composition and alcohol on muscle mass, particularly between sexes, remains scarce.PURPOSETo observe how differences in dietary composition influence the effects of alcohol on skeletal muscle mass in male and female mice.METHODSC57BL/6 mice (n=72; m=36; f=36) aged 12‐weeks‐old were acclimated to a liquid diet for one‐week prior to randomization into either a control (CON: 35% FAT, 47% CHO, 18% PRO) or one of three alcohol (EtOH) treatment groups of differing dietary composition: high‐fat (HF: 35% FAT, 15% CHO, 18% PRO), low‐fat (LF: 12% FAT, 38% CHO, 18% PRO) or high‐protein (PRO: 12% FAT, 31% CHO, 25% PRO). Alcohol was incorporated into the diet and increased over time to a maximum intake of 32% kcal of the diet. Daily consumption of EtOH was assessed relative to body weight. After 7 weeks, the gastrocnemius (GAS) and quadriceps (QUAD) muscles were excised, along with the heart and spleen, which were weighed and expressed relative to body weight. Blood was taken at sacrifice for blood EtOH concentration (BAC); however, feeding status and therefore alcohol intake, was ad libitum up until the time of sample collection. Data were analyzed via 2‐way ANOVA for variables across time, and unpaired t‐tests were used to detect differences between diets and control groups, and between sexes within diets.RESULTSNo significant interactions nor main effects were observed for EtOH consumption between diets within each sex. A significant main effect of sex was observed for EtOH consumption within all diets, where females consumed more EtOH than males (HF: F=71.79, 5.18 ± 0.61 g/kg; LF: F=53.55, 4.37 ± 0.60 g/kg; PRO: F=38.45, 4.75 ± 0.77 g/kg; p’s <0.0001). No main effect of diet was observed for either sex for BAC (p≥0.98) at sacrifice. Female GAS was significantly reduced in HF and LF compared to CON (−8.31 ± 3.74%, p=0.043; −10.53 ± 3.74%, p=0.01 respectively), while no changes were noted for Male GAS. Female QUAD was significantly reduced in HF and LF compared to CON (−10.81 ± 4.52%, p=0.03; −13.63 ± 3.58%, p<0.01 respectively), while no changes were observed for male QUAD. Female heart weights were significantly reduced in HF and LF compared to CON (−12.35 ± 4.33%, p=0.01; −11.34 ± 3.88%, p<0.01 respectively), while an increase in LF was observed in males (9.89 ± 2.55%, p<0.01). Furthermore, female spleen weight was significantly reduced in LF and PRO (−18.39 ± 7.22%, p=0.02; −19.06 ± 6.45%, p=0.01 respectively), while no differences were noted for males.CONCLUSIONSDespite consuming equivalent amounts of EtOH between diets within each sex, females in HF and LF diets experienced significant muscle atrophy compared to CON, while no reductions were observed in PRO. However, this alcohol feeding protocol did not induce significant muscle atrophy in male mice. A possible explanation for these sex differences is that over time, female mice consumed significantly more EtOH relative to body weight than male mice, indicating potential dose‐dependent effects. These sex differences in EtOH preference and resulting alcohol dose require further examination for future work related to the development of alcoholic myopathy.