scholarly journals Edem1 activity in the fat body regulates insulin signalling and metabolic homeostasis in Drosophila

2019 ◽  
Author(s):  
Himani Pathak ◽  
Jishy Varghese
Keyword(s):  
Protein Quality ◽  
Fat Body ◽  
Insulin Signalling ◽  
Nutrient Status ◽  
Vital Role ◽  
Metabolic Homeostasis ◽  
Humoral Factors ◽  
Mammalian Liver ◽  
Nutrient Environment ◽  
Pleiotropic Functions

AbstractIn Drosophila, nutrient status is sensed by the fat body, a functional homolog of mammalian liver and white adipocytes. The fat body conveys nutrient information to insulin-producing cells (IPCs) through humoral factors which regulate Drosophila insulin-like peptide (DILP) levels and insulin signalling. Insulin signalling has pleiotropic functions, which include the management of growth and metabolic pathways. Here, we report that Edem1 (endoplasmic reticulum degradation-enhancing α-mannosidase-like protein 1), an endoplasmic reticulum-resident protein involved in protein quality control, acts in the fat body to regulate insulin signalling and thereby the metabolic status in Drosophila. Edem1 limits the fat body derived Drosophila TNFα Eiger activity on IPCs and maintains systemic insulin signalling in fed conditions. During food deprivation, edem1 gene expression levels drop, which aids in the reduction of systemic insulin signalling crucial for survival. Overall we demonstrate that Edem1 plays a vital role in helping the organism to endure a fluctuating nutrient environment by managing insulin signalling and metabolic homeostasis.

scholarly journals Edem1 activity in the fat body regulates insulin signalling and metabolic homeostasis in Drosophila

2021 ◽  
Vol 4 (8) ◽  
pp. e202101079
Author(s):  
Himani Pathak ◽  
Jishy Varghese
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Quality ◽  
Fat Body ◽  
Insulin Signalling ◽  
Nutrient Status ◽  
Vital Role ◽  
Metabolic Homeostasis ◽  
Humoral Factors ◽  
Insulin Producing Cells ◽  
Factor Α

In Drosophila, nutrient status is sensed by the fat body, a functional homolog of mammalian liver and white adipocytes. The fat body conveys nutrient information to insulin-producing cells through humoral factors which regulate Drosophila insulin-like peptide levels and insulin signalling. Insulin signalling has pleiotropic functions, which include the management of growth and metabolic pathways. Here, we report that Edem1 (endoplasmic reticulum degradation–enhancing α-mannosidase–like protein 1), an endoplasmic reticulum–resident protein involved in protein quality control, acts in the fat body to regulate insulin signalling and thereby the metabolic status in Drosophila. Edem1 limits the fat body–derived Drosophila tumor necrosis factor-α Eiger activity on insulin-producing cells and maintains systemic insulin signalling in fed conditions. During food deprivation, edem1 gene expression levels drop, which aids in the reduction of systemic insulin signalling crucial for survival. Overall, we demonstrate that Edem1 plays a vital role in helping the organism to endure a fluctuating nutrient environment by managing insulin signalling and metabolic homeostasis.

scholarly journals Drosophila Gut—A Nexus Between Dietary Restriction and Lifespan

2018 ◽  
Vol 19 (12) ◽  
pp. 3810 ◽  
Author(s):  
Ting Lian ◽  
Qi Wu ◽  
Brian Hodge ◽  
Kenneth Wilson ◽  
Guixiang Yu ◽  
...  
Keyword(s):  
Digestive Tract ◽  
Dietary Restriction ◽  
Healthy Aging ◽  
Fat Body ◽  
Critical Role ◽  
Vital Role ◽  
Intestinal Epithelial ◽  
Beneficial Effects ◽  
Accumulation Of Damage

Aging is often defined as the accumulation of damage at the molecular and cellular levels which, over time, results in marked physiological impairments throughout the organism. Dietary restriction (DR) has been recognized as one of the strongest lifespan extending therapies observed in a wide array of organisms. Recent studies aimed at elucidating how DR promotes healthy aging have demonstrated a vital role of the digestive tract in mediating the beneficial effects of DR. Here, we review how dietary restriction influences gut metabolic homeostasis and immune function. Our discussion is focused on studies of the Drosophila digestive tract, where we describe in detail the potential mechanisms in which DR enhances maintenance of the intestinal epithelial barrier, up-regulates lipid metabolic processes, and improves the ability of the gut to deal with damage or stress. We also examine evidence of a tissue-tissue crosstalk between gut and neighboring organs including brain and fat body. Taken together, we argue that the Drosophila gut plays a critical role in DR-mediated lifespan extension.

scholarly journals Erratum: Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body

Nature ◽  
2005 ◽  
Vol 434 (7029) ◽  
pp. 118-118 ◽  
Author(s):  
Dae Sung Hwangbo ◽  
Boris Gershman ◽  
Meng-Ping Tu ◽  
Michael Palmer ◽  
Marc Tatar
Keyword(s):  
Fat Body ◽  
Insulin Signalling

scholarly journals Neural clocks and Neuropeptide F/Y regulate circadian gene expression in a peripheral metabolic tissue

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Renske Erion ◽  
Anna N King ◽  
Gang Wu ◽  
John B Hogenesch ◽  
Amita Sehgal
Keyword(s):  
Cytochrome P450 ◽  
Fat Body ◽  
Circadian Gene ◽  
Specific Enzyme ◽  
Rhythmic Expression ◽  
Cytochrome P450 Genes ◽  
Mammalian Liver ◽  
Free Running ◽  
Neuropeptide F ◽  
Systemic Signals

Metabolic homeostasis requires coordination between circadian clocks in different tissues. Also, systemic signals appear to be required for some transcriptional rhythms in the mammalian liver and the Drosophila fat body. Here we show that free-running oscillations of the fat body clock require clock function in the PDF-positive cells of the fly brain. Interestingly, rhythmic expression of the cytochrome P450 transcripts, sex-specific enzyme 1 (sxe1) and Cyp6a21, which cycle in the fat body independently of the local clock, depends upon clocks in neurons expressing neuropeptide F (NPF). NPF signaling itself is required to drive cycling of sxe1 and Cyp6a21 in the fat body, and its mammalian ortholog, Npy, functions similarly to regulate cycling of cytochrome P450 genes in the mouse liver. These data highlight the importance of neuronal clocks for peripheral rhythms, particularly in a specific detoxification pathway, and identify a novel and conserved role for NPF/Npy in circadian rhythms.

scholarly journals The use of Drosophila Melanogaster as a Model Organism to study the effect of Innate Immunity on Metabolism

2020 ◽  
Author(s):  
Abeer Mohbeddin ◽  
Nawar Haj Ahmed ◽  
Layla Kamareddine
Keyword(s):  
Drosophila Melanogaster ◽  
Fat Body ◽  
Model Organism ◽  
Fruit Fly ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Metabolic Homeostasis ◽  
Stat Signaling ◽  
Stat Pathway

Apart from its traditional role in disease control, recent body of evidence has implicated a role of the immune system in regulating metabolic homeostasis. Owing to the importance of this “immune-metabolic alignment” in dictating a state of health or disease, a proper mechanistic understanding of this alignment is crucial in opening up for promising therapeutic approaches against a broad range of chronic, metabolic, and inflammatory disorders like obesity, diabetes, and inflammatory bowel syndrome. In this project, we addressed the role of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) innate immune pathway in regulating different metabolic parameters using the Drosophila melanogaster (DM) fruit fly model organism. Mutant JAK/STAT pathway flies with a systemic knockdown of either Domeless (Dome) [domeG0282], the receptor that activates JAK/STAT signaling, or the signal-transducer and activator of transcription protein at 92E (Stat92E) [stat92EEY10528], were used. The results of the study revealed that blocking JAK/STAT signaling alters the metabolic profile of mutant flies. Both domeG0282 and stat92EEY10528 mutants had an increase in body weight, lipid deprivation from their fat body (lipid storage organ in flies), irregular accumulation of lipid droplets in the gut, systemic elevation of glucose and triglyceride levels, and differential down-regulation in the relative gene expression of different peptide hormones (Tachykinin, Allatostatin C, and Diuretic hormone 31) known to regulate metabolic homeostasis in flies. Because the JAK/STAT pathway is evolutionary conserved between invertebrates and vertebrates, our potential findings in the fruit fly serves as a platform for further immune-metabolic translational studies in more complex mammalian systems including humans.

scholarly journals Large conformational changes in FtsH create an opening for substrate entry

2017 ◽  
Author(s):  
Vanessa Carvalho ◽  
Roland Kieffer ◽  
Nick de Lange ◽  
Andreas Engel ◽  
Marie-Eve Aubin-Tam
Keyword(s):  
Conformational Changes ◽  
Protein Quality ◽  
Atp Hydrolysis ◽  
Transmembrane Helix ◽  
Vital Role ◽  
Full Length ◽  
Aquifex Aeolicus ◽  
Cytosolic Domain ◽  
Central Pore ◽  
Cytoplasmic Structures

AbstractAAA+ proteases are degradation machines, which exploit ATP hydrolysis to unfold protein substrates and translocate them through a central pore towards a degradation chamber. FtsH, a bacterial membrane-anchored AAA+ protease, plays a vital role in membrane protein quality control. Although cytoplasmic structures are described, the full-length structure of bacterial FtsH is unknown, and the route by which substrates reach the central pore remains unclear. We use electron microscopy to determine the 3D map of the full-lengthAquifex aeolicusFtsH hexamer. Moreover, detergent solubilisation induces the formation of fully active FtsH dodecamers, which consist of two FtsH hexamers in a single detergent micelle. FtsH structures reveal that the cytosolic domain can tilt with respect to the membrane. A flexible linker of ~20 residues between the second transmembrane helix and the cytosolic domain permits the observed large tilting movements, thereby facilitating the entry of substrate proteins towards the central pore for translocation.

scholarly journals Insulin signalling in tanycytes gates hypothalamic insulin uptake and regulation of AgRP neuron activity

2021 ◽  
Vol 3 (12) ◽  
pp. 1662-1679
Author(s):  
Marta Porniece Kumar ◽  
Anna Lena Cremer ◽  
Paul Klemm ◽  
Lukas Steuernagel ◽  
Sivaraj Sundaram ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stress Responses ◽  
Arcuate Nucleus ◽  
Protein Quality ◽  
Insulin Signalling ◽  
Critical Role ◽  
Mitochondrial Protein ◽  
Insulin Receptors ◽  
Brain Regions ◽  
Neuron Activity

AbstractInsulin acts on neurons and glial cells to regulate systemic glucose metabolism and feeding. However, the mechanisms of insulin access in discrete brain regions are incompletely defined. Here we show that insulin receptors in tanycytes, but not in brain endothelial cells, are required to regulate insulin access to the hypothalamic arcuate nucleus. Mice lacking insulin receptors in tanycytes (IR∆Tan mice) exhibit systemic insulin resistance, while displaying normal food intake and energy expenditure. Tanycytic insulin receptors are also necessary for the orexigenic effects of ghrelin, but not for the anorexic effects of leptin. IR∆Tan mice exhibit increased agouti-related peptide (AgRP) neuronal activity, while displaying blunted AgRP neuronal adaptations to feeding-related stimuli. Lastly, a highly palatable food decreases tanycytic and arcuate nucleus insulin signalling to levels comparable to those seen in IR∆Tan mice. These changes are rooted in modifications of cellular stress responses and of mitochondrial protein quality control in tanycytes. Conclusively, we reveal a critical role of tanycyte insulin receptors in gating feeding-state-dependent regulation of AgRP neurons and systemic insulin sensitivity, and show that insulin resistance in tanycytes contributes to the pleiotropic manifestations of obesity-associated insulin resistance.

scholarly journals Survival in Hostile Conditions: Pupylation and the Proteasome in Actinobacterial Stress Response Pathways

2021 ◽  
Vol 8 ◽  
Author(s):  
Tatjana von Rosen ◽  
Lena ML Keller ◽  
Eilika Weber-Ban
Keyword(s):  
Stress Responses ◽  
Protein Quality ◽  
Vital Role ◽  
Bacterial Protein ◽  
Core Particle ◽  
Free Living ◽  
Damage Response ◽  
Proteasomal Genes ◽  
Hexameric Atpase ◽  
Living Species

Bacteria employ a multitude of strategies to cope with the challenges they face in their natural surroundings, be it as pathogens, commensals or free-living species in rapidly changing environments like soil. Mycobacteria and other Actinobacteria acquired proteasomal genes and evolved a post-translational, ubiquitin-like modification pathway called pupylation to support their survival under rapidly changing conditions and under stress. The proteasomal 20S core particle (20S CP) interacts with ring-shaped activators like the hexameric ATPase Mpa that recruits pupylated substrates. The proteasomal subunits, Mpa and pupylation enzymes are encoded in the so-called Pup-proteasome system (PPS) gene locus. Genes in this locus become vital for bacteria to survive during periods of stress. In the successful human pathogen Mycobacterium tuberculosis, the 20S CP is essential for survival in host macrophages. Other members of the PPS and proteasomal interactors are crucial for cellular homeostasis, for example during the DNA damage response, iron and copper regulation, and heat shock. The multiple pathways that the proteasome is involved in during different stress responses suggest that the PPS plays a vital role in bacterial protein quality control and adaptation to diverse challenging environments.

scholarly journals Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Luke Stephen Tain ◽  
Robert Sehlke ◽  
Ralf Leslie Meilenbrock ◽  
Thomas Leech ◽  
Jonathan Paulitz ◽  
...  
Keyword(s):  
Dna Damage ◽  
Fat Body ◽  
Insulin Signalling ◽  
Health Improvement ◽  
Proteomic Profiling ◽  
Protein Subunit ◽  
Altered Expression ◽  
Tissue Specific ◽  
Age Related ◽  
Specific Regulation

Reduced activity of the insulin/IGF signalling network increases health during ageing in multiple species. Diverse and tissue-specific mechanisms drive the health improvement. Here, we performed tissue-specific transcriptional and proteomic profiling of long-lived Drosophila dilp2-3,5 mutants, and identified tissue-specific regulation of >3600 transcripts and >3700 proteins. Most expression changes were regulated post-transcriptionally in the fat body, and only in mutants infected with the endosymbiotic bacteria, Wolbachia pipientis, which increases their lifespan. Bioinformatic analysis identified reduced co-translational ER targeting of secreted and membrane-associated proteins and increased DNA damage/repair response proteins. Accordingly, age-related DNA damage and genome instability were lower in fat body of the mutant, and overexpression of a minichromosome maintenance protein subunit extended lifespan. Proteins involved in carbohydrate metabolism showed altered expression in the mutant intestine, and gut-specific overexpression of a lysosomal mannosidase increased autophagy, gut homeostasis, and lifespan. These processes are candidates for combatting ageing-related decline in other organisms.

scholarly journals Insulin signalling regulates remating in female Drosophila

2010 ◽  
Vol 278 (1704) ◽  
pp. 424-431 ◽  
Author(s):  
Stuart Wigby ◽  
Cathy Slack ◽  
Sebastian Grönke ◽  
Pedro Martinez ◽  
Federico C. F. Calboli ◽  
...  
Keyword(s):  
Fat Body ◽  
Insulin Signalling ◽  
Underlying Mechanism ◽  
Neurosecretory Cells ◽  
Dominant Negative ◽  
Developmental Defects ◽  
Mating Rate ◽  
Female Remating ◽  
Reduced Body ◽  
Median Neurosecretory Cells

Mating rate is a major determinant of female lifespan and fitness, and is predicted to optimize at an intermediate level, beyond which superfluous matings are costly. In female Drosophila melanogaster , nutrition is a key regulator of mating rate but the underlying mechanism is unknown. The evolutionarily conserved insulin/insulin-like growth factor-like signalling (IIS) pathway is responsive to nutrition, and regulates development, metabolism, stress resistance, fecundity and lifespan. Here we show that inhibition of IIS, by ablation of Drosophila insulin-like peptide (DILP)-producing median neurosecretory cells, knockout of dilp2 , dilp3 or dilp5 genes, expression of a dominant-negative DILP-receptor ( InR ) transgene or knockout of Lnk , results in reduced female remating rates. IIS-mediated regulation of female remating can occur independent of virgin receptivity, developmental defects, reduced body size or fecundity, and the receipt of the female receptivity-inhibiting male sex peptide. Our results provide a likely mechanism by which females match remating rates to the perceived nutritional environment. The findings suggest that longevity-mediating genes could often have pleiotropic effects on remating rate. However, overexpression of the IIS-regulated transcription factor dFOXO in the fat body—which extends lifespan—does not affect remating rate. Thus, long life and reduced remating are not obligatorily coupled.

Sign in / Sign up

Export Citation Format

Share Document