INS and obesity due to melanocortin 4 receptor deficiency: In line with this, we have recently established that obesity-induced hepatic lipid accumulation increases hepatocyte production and release of the inhibitory neurotransmitter, GABA, in mice (Figure 4A in Geisler et al., 2021 [this issue of Cell Reports]) that we hypothesize acts in a paracrine fashion to decrease the firing activity of the hepatic vagal afferent nerve (HVAN) to regulate insulin secretion and sensitivity (Figure 5 in Geisler et al., 2021).