High-fat diet enhances starvation-induced hyperactivity via sensitizing hunger-sensing neurons in Drosophila

• DOI: 10.7554/elife.53103
• Publication Date: 2020-04-23T12:00:15Z
• Authors: Rui Huang; Tingting Song; Haifeng Su; Zeliang Lai; Wusa Qin; Yinjun Tian; Xuan Dong; Liming Wang
• Keywords: autophagy; QH301-705.5; Hunger; Science; Diet, High-Fat; AKHR; foraging; 03 medical and health sciences; octopamine; Receptors, Glucagon; Animals; Drosophila Proteins; Neurons, Afferent; Biology (General); Neurons; 2. Zero hunger; 0303 health sciences; Q; R; Pyrrolidonecarboxylic Acid; 3. Good health; Starvation; Insect Hormones; Medicine; Drosophila; Oligopeptides; feeding; Neuroscience

The function of the central nervous system to regulate food intake can be disrupted by sustained metabolic challenges such as high-fat diet (HFD), which may contribute to various metabolic disorders. Previously, we showed that a group of octopaminergic (OA) neurons mediated starvation-induced hyperactivity, an important aspect of food-seeking behavior (Yu et al., 2016). Here we find that HFD specifically enhances this behavior. Mechanistically, HFD increases the excitability of these OA neurons to a hunger hormone named adipokinetic hormone (AKH), via increasing the accumulation of AKH receptor (AKHR) in these neurons. Upon HFD, excess dietary lipids are transported by a lipoprotein LTP to enter these OA+AKHR+ neurons via the cognate receptor LpR1, which in turn suppresses autophagy-dependent degradation of AKHR. Taken together, we uncover a mechanism that links HFD, neuronal autophagy, and starvation-induced hyperactivity, providing insight in the reshaping of neural circuitry under metabolic challenges and the progression of metabolic diseases.