The impact of a high-fat diet in mice is dependent on duration and age, and differs between muscles

Prolonged high-fat diets (HFD) can cause intramyocellular lipids (IMCL) accumulation that may negatively affect muscle function. We investigated the duration of a HFD required to instigate these changes, and whether effects are muscle-specific and aggravated in older age. Muscle morphology was determined in the soleus, extensor digitorum longus (EDL) and diaphragm muscles from female CD-1 mice divided into 5 groups: young fed a HFD for 8 weeks (YS-HFD, n=16), young fed a HFD for 16 weeks (YL-HFD, n=28) and young control (Y-CON, n=28). The young animals were 20 weeks old at the end of the experiment. Sixty 70-week-old female CD-1 mice received either a normal diet (O-CON, n=30) or a HFD for 9 weeks (OS-HFD, n=30). Body mass, body mass index and IMCL content increased in old OS-HFD (p≤0.003). In the young mice, this increase was seen in YL-HFD and not YS-HFD (p≤0.006). The soleus and diaphragm fibre cross-sectional area (FCSA) in YL-HFD was larger compared to Y-CON (p≤0.004) while old mice had a larger soleus FCSA compared to CON after only 9 weeks on a HFD (p<0.001). The FCSA of the EDL muscle did not differ significantly between groups. Oxidative capacity of fibres increased in young only, irrespective of HFD duration (p<0.001). High-fat diet-induced morphological changes occur earlier in the old animals when compared to young, and adaptations to HFD are muscle-specific with the EDL being least responsive.