Figure 3: Conceptual model for hypothalamic lipophagy in control of food intake. In the fed state, active PI3K/mTOR signaling maintains autophagy at basal lower levels. Starvation increases circulating free fatty acids (FFAs), which activate hypothalamic autophagy by mechanisms that may in part require activation of AMPK/ULK1. These FFAs taken up by hypothalamic neurons are rapidly esterified into neutral lipids within lipid droplets. Activation of hypothalamic autophagy mobilizes neuronal lipids for the controlled availability of neuron-intrinsic FFAs that increase AgRP expression and food intake. AgRP: Agouti-related peptide, AMPK: AMP-activated protein kinase, FFA: free fatty acids, LD: lipid droplets, PI3K: phosphoinositide 3-kinase, mTOR: mammalian target of rapamycin, and ULK1: unc-51-like kinase 1.