However, previous studies from our group [48] showed a decrease in insulin receptor and IRS-1 tyrosine phosphorylation in morbid obese patients with severe NASH, which suggests that at some point in the progression of NAFLD, a continuous overstimulation of insulin receptor may lead to impairment in insulin signaling more proximally in the cascade. This evidence concerns the gene IRS1 and metabolic dysfunction-associated steatotic liver disease.