Drosophila insulin-like peptide dilp1 increases lifespan and glucagon-like Akh expression epistatic to dilp2

Post, Stephanie; Liao, Sifang; Yamamoto, Rochele; Vennstra, Jan A; Nässel, Dick R.; Tatar, Marc

doi:10.1101/380410

Cited by 7 publications

(9 citation statements)

References 45 publications

(75 reference statements)

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“…Several secreted proteins also have been reported to regulate AKH secretion. dILP2 induces AKH expression in CC in a dILP1-dependent fashion in adult Drosophila (102). Similarly, Upd2 secreted from skeletal muscle promotes AKH secretion from CC in adults (20).…”

Section: Regulation Of Akh Signalingmentioning

confidence: 95%

What fuels the fly: Energy metabolism in Drosophila and its application to the study of obesity and diabetes

2021

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The organs and metabolic pathways involved in energy metabolism, and the process of ATP production from nutrients, are comparable between humans and Drosophila melanogaster. This level of conservation, together with the power of Drosophila genetics, makes the fly a very useful model system to study energy homeostasis. Here, we discuss the major organs involved in energy metabolism in Drosophila and how they metabolize different dietary nutrients to generate adenosine triphosphate. Energy metabolism in these organs is controlled by cell-intrinsic, paracrine, and endocrine signals that are similar between Drosophila and mammals. We describe how these signaling pathways are regulated by several physiological and environmental cues to accommodate tissue-, age-, and environment-specific differences in energy demand. Last, we discuss several genetic and diet-induced fly models of obesity and diabetes that can be leveraged to better understand the molecular basis of these metabolic diseases and thereby promote the development of novel therapies.

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Section: Regulation Of Akh Signalingmentioning

confidence: 95%

What fuels the fly: Energy metabolism in Drosophila and its application to the study of obesity and diabetes

2021

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“…Crz is released during stress to mobilize energy stores and fuel locomotion, it could also act on Va neurons to stimulate CAPA release, which would aid in expulsion of metabolic waste 18 products via the Malpighian tubules. Moreover, Crz could also independently modulate CAPA release during desiccation and cold stress.…”

Section: How Does Systemic Crz Signaling To the Capa-expressing Va Nementioning

confidence: 99%

“…Although the insect pars intercerebralis-pars lateralis and corpora cardiaca are considered the functional equivalents of mammalian hypothalamus and pituitary gland, respectively [16], no explicit stress axis or stress hormones have yet been identified in insects. Much progress has been made on the roles of DILPs and AKH (insect ortholog of mammalian gonadotropin-releasing hormone; GnRH) in metabolism, nutritional stress and longevity [5,10,[17][18][19]. For instance, both these signaling systems regulate starvation-induced hyperactivity/food search in Drosophila [20].…”

Section: Introductionmentioning

confidence: 99%

A neuroendocrine pathway modulating osmotic stress inDrosophila

Zandawala

Nguyen

Segura

et al. 2019

Preprint

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Environmental factors challenge the physiological homeostasis in animals, thereby evoking stress responses. Various mechanisms have evolved to counter stress at the organism level, including regulation by neuropeptides. Corazonin (Crz) is a neuropeptide known to regulate stress-associated physiology in Drosophila. However, the neural circuits and hormonal pathways underlying this regulation are poorly known. To unveil targets of Crz, we mapped the Crz receptor (CrzR) expression in Drosophila central nervous system (CNS).The CrzR is expressed in peptidergic neurons in the adult CNS, including the median neurosecretory cells and certain clock neurons in the brain, Hugin neurons in the subesophageal zone (SEZ) and CAPA-expressing neurosecretory cells in the SEZ and abdominal neuromeres (Va neurons). We focused on the Va neurons since they produce osmoregulatory peptides (CAPA-1 and CAPA-2), which mediate recovery from desiccation and cold stress. Trans-Tango labeling to determine synaptic partners failed to reveal connections between Crz and Va neurons, suggesting hormonal interactions. To validate the signaling between Crz and Va neurons, we show that knockdown of Crz in Crzproducing neurons and CrzR in Va neurons increases survival under desiccation and delays chill coma recovery. Moreover, immunolabeling data suggests that Crz is released under nutritional and osmotic stress, and in vivo Crz peptide injections influence responses to desiccation and chill coma. Thus, Crz modulates Va neurons to maintain osmotic/ionic homeostasis, which in turn influences stress tolerance. Taken together with previous data, we propose that Crz acts via both the fat body and peptidergic neurons in the CNS to regulate stress-associated physiology.

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“…The dilp1 mutant flies have normal lifespan, and so do dilp1-dilp2 double mutants, suggesting that loss of dilp1 rescues the lifespan extension of dilp2 mutants. This study also found that dilp1 is downstream of dilp2 in regulation of AKH [535], another known positive regulator of longevity [533]. It was suggested that DILP2 indirectly regulates AKH by repressing expression of DILP1 (that normally upregulates AKH) and also that DILP1 normally represses JH, which results in prolongevity effects [535].…”

Section: 1 4 Insulin Signaling In Lifespan and Diapausesupporting

confidence: 55%

“…Also some other gene manipulations that decrease dilp2 expression increase lifespan: overexpression of FOXO in the fat body and JNK in the IPCs [634][635][636]. In contrast, it was recently shown that dilp1 promotes longevity [535]. The dilp1 mutant flies have normal lifespan, and so do dilp1-dilp2 double mutants, suggesting that loss of dilp1 rescues the lifespan extension of dilp2 mutants.…”

Section: 1 4 Insulin Signaling In Lifespan and Diapausementioning

confidence: 99%

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Supplemental Information 1: Supplementary Table 1

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This review focuses on neuropeptides and peptide hormones, the largest and most diverse class of neuroactive substances, known in Drosophila and other animals to play roles in almost all aspects of daily life, as well as in developmental processes.We provide an update on novel neuropeptides and receptors identified in the last decade, and highlight progress in analysis of neuropeptide signaling in Drosophila.Especially exciting is the huge amount of work published on novel functions of neuropeptides and peptide hormones in Drosophila, largely due to the rapid developments of powerful genetic methods, imaging techniques and innovative assays. We critically discuss the roles of peptides in olfaction, taste, foraging, feeding, clock function/sleep, aggression, mating/reproduction, learning and other behaviors, as well as in regulation of development, growth, metabolic and water homeostasis, stress responses, fecundity, and lifespan. We furthermore provide novel information on neuropeptide distribution and organization of peptidergic systems, as well as the phylogenetic relations between Drosophila neuropeptides and those of other phyla, including mammals. As will be shown, neuropeptide signaling is phylogenetically ancient, and not only are the structures of the peptides,

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Drosophila insulin-like peptide dilp1 increases lifespan and glucagon-like Akh expression epistatic to dilp2

Cited by 7 publications

References 45 publications

What fuels the fly: Energy metabolism in Drosophila and its application to the study of obesity and diabetes

What fuels the fly: Energy metabolism in Drosophila and its application to the study of obesity and diabetes

A neuroendocrine pathway modulating osmotic stress inDrosophila

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