In a randomized, double-blinded, placebo-controlled study, Charles et al. showed a positive dose-dependent relationship between PEGylated FGF21 analog treatment and serum adiponectin levels in obese patients with type 2 diabetes and NAFLD while no significant change in HOMA-IR was observed (27) Their findings provide direct evidence that FGF21 has a substantial role in the regulation of circulating adiponectin concentrations even in the absence of a change in insulin resistance state. This evidence concerns the gene ADIPOQ and Insulin resistance.