LEP and diabetes mellitus: 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.