Incubation of HepG2 with HSPs or serum from obese IR, NAFLD subjects inhibited Akt phosphorylation on Ser473 (Fig. 4a–c) and insulin-mediated glucose uptake (Fig. 4d–f), while no effect was detected after stimulation with serum depleted of HSP70 or GRP78. Here, HSPA5 is linked to metabolic dysfunction-associated steatotic liver disease.