The effect of myo-inositol supplementation on AMPK/PI3K/AKT pathway and insulin resistance in patients with NAFLD.

Insulin resistance (IR) is the pivotal pathological hit in non-alcoholic fatty liver disease (NAFLD). There is specific attention to combination/conjugated therapies for NAFLD management. As myo-inositol (MI) has been shown to improve IR in animal and human trials, this study aimed to investigate the influence of MI supplementation on glycemic response and IR through AMPK/PI3K/AKT signaling pathway in obese patients with NAFLD. This double-blinded placebo-controlled randomized clinical trial was conducted on 48 obese (BMI = 30-40 kg/m) patients with NAFLD who were randomly assigned to receiving either MI (4 g/day) or placebo (maltodextrin 4 g/day) group for 8 weeks. Before and after the trial, weight, height, serum glycemic parameters (inc. fasting glucose and insulin) as well as IR indices were assessed. Moreover, the mRNA expression levels of AMPK, AKT, and PDK-1 in peripheral blood mononuclear cells (PBMCs) were determined. MI supplementation resulted in significant increases in the fold changes of AMPK, AKT, and PDK-1 genes ( = .019,  = .049, and  = .029, respectively). Indeed, IR improved in terms of all IR indices in MI group ( < .05) after adjusting for the confounders, apart from quantitative insulin sensitivity check index (QUICKI). The results showed that MI supplementation not only upregulated AMPK, AKT, and PDK-1 mRNA in PBMCs but also improved IR in obese patients with NAFLD.