The insulin-like peptide (ILP) family plays key biological roles in the control of body growth. Although the functions of ILPs are well understood, the mechanisms by which organisms sense their ...nutrient status and thereby control ILP production remain largely unknown. Here, we show that signaling relay and feedback mechanisms control the nutrient-dependent expression of Drosophila ILP5 (Dilp5). The expression of dilp5 in brain insulin-producing cells (IPCs) is negatively regulated by the transcription factor FoxO. Glia-derived Dilp6 remotely regulates the FoxO activity in IPCs, primarily through Jeb secreted by cholinergic neurons. Dilp6 production by surface glia is amplified by cellular response to circulating Dilps derived from IPCs, in concert with amino acid signals. The induction of dilp5 is critical for sustaining body growth under restricted food conditions. These results provide a molecular framework that explains how the production of an endocrine hormone in a specific tissue is coordinated with environmental conditions.
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•Nutrient-dependent dilp5 expression is negatively regulated by FoxO in brain IPCs•FoxO activity is regulated by Alk, and its ligand Jeb is secreted by cholinergic neurons•Glia-derived Dilp6 remotely initiates dilp5 expression through cholinergic neurons•The induction of dilp5 is critical to sustain body growth under restricted food
Insulin-like peptides (ILPs) play key roles in the control of body growth in response to nutrient status. Okamoto and Nishimura now demonstrate the signaling relay and feedback mechanisms by which insulin-producing cells sense nutritional signals and thereby control the production of an ILP in the fruit fly Drosophila melanogaster.
Ecdysteroids are a class of steroid hormones in arthropods that control molting and metamorphosis through interaction with intracellular nuclear receptors. In contrast to the extensive literature ...describing their biosynthetic pathways and signaling components, little has been known about how these hormones are traveling into and out of the cells through lipid bilayers of the cell membranes. Recently, a series of studies conducted in the fruit fly Drosophila melanogaster revealed that membrane transporters have critical functions in trafficking ecdysteroids across cell membranes, challenging the classical simple diffusion model of steroid hormone transport. Here we summarize recent advances in our understanding of membrane transporters involved in ecdysteroid signaling in Drosophila, with particular focus on Ecdysone Importer (EcI) that is involved in ecdysteroid uptake in peripheral tissues. We then discuss the potential advantage of EcI blockers as a novel pest management tool as compared to classical insect growth regulators.
In multicellular organisms, endocrine factors such as hormones and cytokines regulate development and homoeostasis through communication between different organs. For understanding such interorgan ...communications through endocrine factors, the fruit fly Drosophila melanogaster serves as an excellent model system due to conservation of essential endocrine systems between flies and mammals and availability of powerful genetic tools. In Drosophila and other insects, functions of neuropeptides or peptide hormones from the central nervous system have been extensively studied. However, a series of recent studies conducted in Drosophila revealed that peptide hormones derived from peripheral tissues also play critical roles in regulating multiple biological processes, including growth, metabolism, reproduction, and behaviour. Here, we summarise recent advances in understanding target organs/tissues and functions of peripherally derived peptide hormones in Drosophila and describe how these hormones contribute to various biological events through interorgan communications.
Evolutionarily conserved insulin/insulin-like growth factor (IGF) signaling (IIS) has been identified as a major physiological mechanism underlying the nutrient-dependent regulation of sexually ...selected weapon growth in animals. However, the molecular mechanisms that couple nutritional state with weapon growth remain largely unknown. Here, we show that one specific subtype of insulin-like peptide (ILP) responds to nutrient status and thereby regulates weapon size in the broad-horned flour beetle Gnatocerus cornutus. By using transcriptome information, we identified five G. cornutus ILP (GcorILP1-5) and two G. cornutus insulin-like receptor (GcorInR1, -2) genes in the G. cornutus genome. RNA interference (RNAi)-mediated gene silencing revealed that a certain subtype of ILP, GcorILP2, specifically regulated weapon size. Importantly, GcorILP2 was highly and specifically expressed in the fat body in a condition-dependent manner. We further found that GcorInR1 and GcorInR2 are functionally redundant but that the latter is partially specialized for regulating weapon growth. These results strongly suggest that GcorILP2 is an important component of the developmental mechanism that couples nutritional state to weapon growth in G. cornutus. We propose that the duplication and subsequent diversification of IIS genes played a pivotal role in the evolution of the complex growth regulation of secondary sexual traits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The quality of oocytes declines by aging, resulting in their low competences for fertility. Here, resveratrol treatment showed increases in the rates of implantation and live offspring as well as ...decreases in the abortion rate as short as one week after treatment, although the number of ovulated oocytes and the rates of fertilization and blastocyst formation were not changed following resveratrol treatment. Resveratrol treatment did not cause abnormalities mouse estrous cycles and body weights. No abnormality was detected in both fetuses and placentas after 22 weeks of resveratrol treatment and the fetuses had normal fertility. Positive correlations were found between serum resveratrol levels and pregnancy and live offspring rates as well as ovarian expression levels of
,
,
,
, and
. The mitochondrial membrane potential and ATP content but not copy number of mitochondrial DNA in oocytes was increased in aging mice with resveratrol treatment. In conclusion, we demonstrated the restoration of oocyte quality in aging mice in addition to the prevention of their quality decline during aging by restoring mitochondrial functions by resveratrol treatment without adverse effects in the animals and their offspring.
Isoliquiritigenin, a component of Glycyrrhiza uralensis, is a potent inhibitor of the NLRP3 inflammasome, and suppresses diet‐induced obesity, adipose tissue inflammation, and metabolic disorders.
...Inflammasome activation initiates the development of many inflammatory diseases, including obesity and type 2 diabetes. Therefore, agents that target discrete activation steps could represent very important drugs. We reported previously that ILG, a chalcone from Glycyrrhiza uralensis, inhibits LPS‐induced NF‐κB activation. Here, we show that ILG potently inhibits the activation of NLRP3 inflammasome, and the effect is independent of its inhibitory potency on TLR4. The inhibitory effect of ILG was stronger than that of parthenolide, a known inhibitor of the NLRP3 inflammasome. GL, a triterpenoid from G. uralensis, had similar inhibitory effects on NLRP3 activity, but high concentrations of GL were required. In contrast, activation of the AIM2 inflammasome was inhibited by GL but not by ILG. Moreover, GL inhibited NLRP3‐ and AIM2‐activated ASC oligomerization, whereas ILG inhibited NLRP3‐activated ASC oligomerization. Low concentrations of ILG were highly effective in IAPP‐induced IL‐1β production compared with the sulfonylurea drug glyburide. In vivo analyses revealed that ILG potently attenuated HFD‐induced obesity, hypercholesterolemia, and insulin resistance. Furthermore, ILG treatment improved HFD‐induced macrovesicular steatosis in the liver. Finally, ILG markedly inhibited diet‐induced adipose tissue inflammation and IL‐1β and caspase‐1 production in white adipose tissue in ex vivo culture. These results suggest that ILG is a potential drug target for treatment of NLRP3 inflammasome‐associated inflammatory diseases.
Chronic activation of the IL‐1β system in adipose tissue on metabolic disorders is well demonstrated. However, a mechanism for its expression and activation in the tissue has remained unexplored. ...Here, we demonstrate that IL‐1β transcript was enriched in neutrophils of white adipose tissue (WAT) from lean mice. Mechanistically, the interaction of neutrophils with adipocytes induced IL‐1β expression via NF‐κB pathway. Lipolysis of adipocytes accumulated neutrophils prior to macrophages in WAT and produced high levels of IL‐1β via an inflammasome pathway. Leukotriene B4 (LTB4) production in WAT also contributed to neutrophil accumulation. Furthermore, an LTB4‐inflammasome axis contributed to the expression of chemotactic molecules involved in high‐fat diet‐induced macrophage infiltration into WAT. We have identified previously unappreciated roles for neutrophils in the development of adipose tissue inflammation: robust IL‐1β production and infiltration of macrophages to initiate chronic inflammation.—Watanabe, Y., Nagai, Y., Honda, H., Okamoto, N., Yanagibashi, T., Ogasawara, M., Yamamoto, S., Imamura, R., Takasaki, I., Hara, H., Sasahara, M., Arita, M., Hida, S., Taniguchi, S., Suda, T., Takatsu, K. Bidirectional crosstalk between neutrophils and adipocytes promotes adipose tissue inflammation. FASEB J. 33, 11821‐11835 (2019). www.fasebj.org
Pregnancy rate of women decreases with age due to declining quality of oocytes and embryos. However, there is no established method to improve pregnancy rate in aging women. In this study, we ...identified a senescence‐associated secretory phenotype (SASP) factor partially responsible for the decline in embryo implantation potential. Based on microarray analysis using young and aging human embryos at the same morphological grade, 702 genes showed >fivefold increases in aging human blastocysts. Among these genes, C‐X‐C motif chemokine 5 (CXCL5) showed 7.7‐fold increases in aging human blastocysts. However, no‐age‐dependent changes in expression of the CXCR2, the cognate receptor for CXCL5, were found. In aging mice, Cxcl5 transcript levels were also increased in oocytes and embryos. Treatment of young mouse embryos with CXCL5 decreased implantation rates, together with increased expression of aging markers (P53, P21, Pai‐1, and Il‐6). Moreover, CXCL5 treatment suppressed trophoblast outgrowth in young mouse blastocysts. Conversely, suppression of CXCL5‐CXCR2 signaling in aging mouse embryos using neutralizing antibodies and a receptor antagonist improved the implantation rate, leading to increases in pregnancy and delivery of normal pups. The gene expression pattern of these embryos was comparable to that in young mouse embryos showing enriched cell proliferation‐related pathways. In conclusion, we identified CXCL5 as a SASP factor in human and mouse embryos and suppression of CXCL5‐CXCR2 signaling during embryo culture improved pregnancy success in aging mice. Future analysis on CXCL5‐CXCR2 signaling suppression in human embryos could be the basis to improve embryo development and pregnancy outcome in middle‐aged infertile patients.
We identified CXCL5 as a senescence‐associated secretory phenotype (SASP) factors in preimplantation embryos, showing elevated expression in embryos of older women and mice. The implantation rate of CXCL5‐treated young embryos from mice was decreased due to suppression of trophoblast cell proliferation. In aging embryos, suppression of CXCL5‐CXCR2 signaling during embryo culture might improve pregnancy outcome for middle‐aged women undergoing IVF.
Bismuth is considered one of the promising anode materials for the magnesium-ion secondary battery (MIB), but it has a short cycle life because of the sluggish diffusion of Mg
2+
into the Bi anode ...and the slow interfacial charge transfer. In this study, we employed electrodeposition as a simple method to deposit the Bi thin films as an anode material for MIB and tried to control the surface structure of the films. In addition, we measured the deposition behavior while varying experimental parameters. The crystallographic structure, surface morphology, and electrochemical performance of the Bi anodes were evaluated by X-ray diffraction, scanning electron microscopy, and a charging/discharging control device, respectively. Then, the relationships between the physical properties and charging/discharging characteristics of the Bi anode were investigated. In particular, a Bi electrode with the thickness of 1.5 μm deposited at a density of 10 mA/cm
2
showed good cycling capability; its capacity at the 50th cycle was 101 mAh/g.
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