Pioglitazone (PIO), a diabetes drug, improves the effect of insulin/leptin in the hypothalamus, partly by activating the Adipo/AdipoR1/AMPK axis in the hypothalamus (Quaresma et al., 2016), suggesting that Adipo and AdipoR1 may play an important role in improving the effect of IR in hypothalamus. Here, INS is linked to diabetes mellitus.