Aim: To determine the prevalence of skeletal muscle alterations (SMA) in patients with meta-bolic dysfunction-associated steatotic liver disease (MASLD) and to assess the significance of circulating myokines as potential biomarkers of SMA in patients with MASLD. Material and methods: Measurements of both skeletal muscle strength and skeletal muscle mass parameters, anthropometric and metabolic features as well as serum levels of different myokines were per-formed in a cohort of 62 MASLD patients and then compared according to the stage of liver fi-brosis and hepatosteatosis degree both diagnosed by transitional elastography. Results: No sig-nificant differences were found in skeletal muscle strength and skeletal muscle mass in MASLD patients stratified according to the stage of liver fibrosis. Noteworthy, serum levels of FGF21 were significantly higher in MASLD patients with advanced hepatic fibrosis (F3-F4) than in those with lower stages of hepatic fibrosis (F0-F2) (197.49±198.27 pg/ml vs 95.62±83.67 pg/ml, p=0.049, respectively). MASLD patients with severe hepatosteatosis (S3) had significantly higher serum levels of irisin (1116.87±1161.86 pg/ml) than those with lower grades (S1-S2) (385.21±375.98 pg/ml, p=0.001). Conclusion: SMA were uncommon in our MASLD patients, particularly in those with lower stages of liver fibrosis. An increase in serum FGF21 was detected in patients with a higher stage of fibrosis with possible therapeutic implications in MASLD.

Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.