Biology subjects

Post, S.

Publications and source records attributed to Post, S..

3 recordsLinked to original sources

bioRxiv2018

Drosophila insulin-like peptide 1 (DILP1) promotes organismal growth during non-feeding stages

The insulin/IGF-signaling pathway is central in control of nutrient-dependent growth during development, and in adult physiology and longevity. Eight insulin-like peptides (DILP1-8) have been identified in Drosophila and several of these are known to regulate growth, metabolism, reproduction, stress responses and lifespan. However, the functional role of DILP1 is far from understood. Previous work has shown that dilp1/DILP1 is transiently expressed mainly during the non-feeding pupal stage and the first days of adult life. Here we show that mutation of dilp1 diminishes organismal weight during pupal development, whereas overexpression increases it, similar to dilp6 manipulations. No growth effects of dilp1 or dilp6 manipulations were detected during larval development. We next show that dilp1 and dilp6 increase metabolic rate in the late pupa and promote lipids as the primary source of catabolic energy. This lipid mobilization in the pupa is not correlated with transcriptional changes of adipokinetic hormone. The effects of dilp1 manipulations carry over to the adult fly. In newly eclosed flies, survival during starvation is strongly diminished in dilp1 mutants, but not in dilp2 and dilp1-dilp2 double mutants, whereas in older flies only double mutants display reduced starvation resistance. In conclusion, dilp1 and dilp6 promote growth of adult tissues during the non-feeding pupal stage, likely by utilization of stored lipids. This results in larger newly-eclosed flies with reduced stores of pupal-derived nutrients and diminished starvation tolerance and fecundity.

neuroscience↗

bioRxiv2018

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

Insulin/IGF signaling (IIS) regulates essential processes including development, metabolism, and aging. The Drosophila genome encodes eight insulin/IGF-like peptide (dilp) paralogs, including tandem-encoded dilp1 and dilp2. Many reports show that longevity is increased by manipulations that decrease DILP2 in adults. In contrast, dilp1 is expressed primarily in pupal stages, but also during adult reproductive diapause, although we find that dilp1 is also highly expressed in adult dilp2 mutants under non-diapause conditions. The inverse expression of dilp1 and dilp2 suggests these genes interact to regulate aging. Here, we study dilp1 and dilp2 single and double mutants to describe epistatic and synergistic interactions affecting longevity, metabolism and adipokinetic hormone (AKH), a functional homolog of glucagon. Mutants of dilp2 extend lifespan and increase Akh mRNA and protein in a dilp1-dependent manner. Loss of dilp1 alone has no impact on these traits, whereas transgene expression of dilp1 increases lifespan in dilp1-dilp2 double mutants. On the other hand, dilp1 and dilp2 redundantly interact to control circulating sugar, starvation resistance and compensatory dilp5 expression. These later interactions do not correlate with patterns for how dilp1 and dilp2 affect longevity and AKH. Thus, repression or loss of dilp2 slows aging because its depletion induces dilp1, which acts as a pro-longevity factor. Likewise, dilp2 regulates Akh through epistatic interaction with dilp1. Akh and glycogen affect aging in C. elegans and Drosophila, suggesting that dilp2 modulates lifespan via dilp1 and in part by regulating Akh. Whether DILP1 acts as an insulin receptor agonist or inhibitor remains to be resolved.

physiology↗

bioRxiv2017

Drosophila Kruppel homolog 1 represses lipolysis through interaction with dFOXO

Transcriptional coordination is a vital process contributing to metabolic homeostasis. As one of the key nodes in the metabolic network, the forkhead transcription factor FOXO has been shown to interact with diverse transcription co-factors and integrate signals from multiple pathways to control metabolism, oxidative stress response, and cell cycle. Recently, insulin/FOXO signaling has been implicated in the regulation of insect development via the interaction with insect hormones, such as ecdysone and juvenile hormone. In this study, we identified an interaction between dFOXO and the zinc finger transcription factor Kruppel homolog 1 (Kr-h1), one of the key players in juvenile hormone signaling in Drosophila. We found that Kr-h1 mutants have reduced triglyceride storage, decreased insulin signaling and delayed larval development. Notably, Kr-h1 physically and genetically interacts with dFOXO in vitro and in vivo to regulate the transcriptional activation of adipose lipase brummer (bmm). The transcriptional co-regulation by Kr-h1 and dFOXO may represent a broad mechanism by which Kruppel-like factors integrate with insulin signaling to maintain metabolic homeostasis and coordinate organism growth.

genetics↗