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

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>Proper regulation of food intake can be disrupted by sustained metabolic challenges such as high-fat diet (HFD), which may result in various metabolic disorders. Previously, we showed that starvation induced sustained hyperactivity, an exploratory component of food-seeking behavior, via a specific group of octopamingeric (OA) neurons (Yu et al., 2016). In the present study, we found that HFD greatly enhanced starvation-induced hyperactivity. HFD increased 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 were transported by a lipoprotein LTP to enter these OA neurons via the cognate receptor LpR1, which activated AMPK-TOR signaling and suppressed autophagy-dependent degradation of AKHR. Taken together, we uncovered a mechanism that linked HFD and starvation-induced hyperactivity, providing insight in the reshaping of neural circuitry under metabolic challenges and the progression of metabolic diseases.</jats:p>

Fat Body Phospholipid State Dictates Hunger Driven Feeding Behavior

“…However, the response of HSD flies to Hunger Driven Feeding (HDF) is present after a short period of exposure, but is lost after a chronic exposure of 14 days. While feeding behavior measurements have not been measure past 10 days, our acute data is in line with previous literature as we do note an increase in baseline feeding in HSD after acute exposure which has been previously reported 17,50 . However, by 14 days of HSD, we find flies lose their HDF and show a similar response to food as ad libitum fed.…”

“…One example of such a factor is leptin, which is released from the adipose tissue and acts on neuronal circuits in the brain to promote satiety 79,80 . While Leptin has long been studied as a satiety hormone, recent work in mice and in flies suggests that a key function of leptin and its fly homolog upd2 is to regulate starvation response 10,79,81,82 . Indeed, we have previously shown that exposing flies to HSD alters synaptic contacts between Leptin/Upd2 sensing neurons and Insulin neurons, however, it resets within 5-days 10 .…”

Sex determination gene transformer regulates the male-female difference in Drosophila fat storage via the adipokinetic hormone pathway

“…Indeed, augmenting APC activity in females using a bacterial voltage-gated sodium channel (UAS-NaChBac) significantly reduced fat storage in females (Figure 4F; Figure 4 -figure supplement 3E). While Akh affects food-related behaviours in some contexts (Choi et al, 2015;Hentze et al, 2015;Huang et al, 2020), we observed no significant effects of altered APC activity on feeding behaviour in either sex (Figure 4 -figure supplement 4A-D). This suggests that the male-biased effect of APC manipulation on fat storage cannot be fully explained by effects on food intake.…”

Adipokinetic hormone signaling regulates cytochrome P450‐mediated chlorantraniliprole sensitivity in Spodoptera frugiperda (Lepidoptera: Noctuidae)

“…The ligand adipokinetic hormone (AKH) synthesized and released by the corpora cardiaca (CC) and AKH receptor (AKHR) as rhodopsin‐like GPCR has been proven to be involved in the regulation of energy metabolism, feeding, reproduction, diapause, flight and other activities. Particularly under stress conditions, AKH and AKHR can couple and participate in antioxidant stress responses by activating AC, PKA and cAMP 37–45 . Recent studies have shown that AKH and its receptor AKHR are involved in regulating resistance to insecticides 38,46–49 .…”