GSE129602
High-fat diet enhances food-seeking behavior via sensitizing hunger-sensing neurons in Drosophila II
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 the development of various metabolic disorders. In the present study, we found that HFD specifically enhanced food-seeking behavior in fruit flies without altering flies' baseline metabolism and food consumption. Mechanistically, HFD increased the excitability of a small group of octopaminergic (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 activated AMPK-TOR signaling and suppressed autophagy-dependent degradation of AKHR. Taken together, we uncovered a mechanism that linked HFD, AMPK-TOR signaling, neuronal autophagy, and food-seeking behavior, providing insight in the reshaping of neural circuitry under metabolic challenges and the progression of metabolic diseases. Overall design: Total RNA from fly heads was extracted from 5-day-old female flies using the Trizol reagent (Invitrogen, USA), subjected to poly(A) mRNA isolation, cDNA synthesization, library preparation (NEBNext Ultra RNA Library Prep Kit, NEB), and sequencing (Illumina Hiseq2500/4000 platform). Sequence data were subsequently mapped to Drosophila genome and uniquely mapped reads were collected for further analysis. Gene expression was calculated by the RPKM (Reads Per Kilobase of exon per Million reads mapped). The genes with p-value less 0.05 and fold change more than 2 were considered as the differentially expressed gene.