Obesity Impacts the Histological Features and Modifies the Apelin Levels in Different Skeletal Muscles of Aging Female Wistar Rat

The aim was to evaluate the apelinergic system (Apln/Aplnr) levels, and the TEAD1-YAP intracellular signalling via , as well as the histological parameters of three muscles (soleus [Sol], gastrocnemius [Ga], and extensor digitorum longus [Edl]) of the aging female Wistar rats fed with a high-fat diet (HFD). Two groups of seven ageing female Wistar rats were randomly assigned to the control (Ctrl) or obesity (Ob) groups and fed a chow diet or an HFD from day 21 until 650 days old. In Sol, Ga, and Edl muscle tissues, we evaluated the lipids, area, and size distribution of muscle fibres, the percentage of fibre types I and II (a and b), and the proteins Apln, Aplnr, Tead1, and YAP (total and phosphorylated). We found a significant increase in the percentage of lipid-positive cells in the cross-sectional area of the Sol and Edl muscles (p=0.044 and p=0.003, respectively) in the Ob group, and a decrease in the area of the Sol with an increase in the Edl muscle area (p=0.0004 and p=0.0160, respectively). We did not find significant differences in the percentages of type I, IIa, and IIb fibres across the three muscles analyzed. We observed a decrease in Apln protein levels in the Ob group in the Ga muscle (p=0.002). In conclusion, our study provides new insights into the impact of aging and obesity, which varies by muscle type and involves morphological changes in fibre size, lipid accumulation, and alterations in Apln levels. Skeletal muscle changes with aging and obesity, with distinct effects across muscles. Whereas the soleus muscle (oxidative metabolism) showed decreased fiber size, the gastrocnemius muscle showed no apparent changes. Still, the Edl muscle (glycolytic metabolism) showed increased fibre size and fiber-type turnover. This indicates a muscle-dependent impact of obesity. Moreover, Apln levels are decreased only in the gastrocnemius muscle of the Ob group; however, their receptor (Aplnr) and the Yap-Tead1 pathway are not altered. Therefore, the modulation of Apln in this model (female) is not mediated by Yap-Tead1 factors. • Obesity affects the histomorphology of skeletal muscle in ageing female rats. • Obesity alters apelin protein levels in the muscle of aging female rats. • The effects of obesity on skeletal muscle in the aging context vary depending on the muscle's contractile and biochemical characteristics.