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 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 Communications between Mitochondria and Endoplasmic Reticulum in the Regulation of Metabolic Homeostasis

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2195
Author(s):  
Pengcheng Zhang ◽  
Daniels Konja ◽  
Yiwei Zhang ◽  
Yu Wang
Keyword(s):  
Endoplasmic Reticulum ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Metabolic Diseases ◽  
Nutrient Status ◽  
Signaling Molecules ◽  
Metabolic Homeostasis ◽  
Contact Sites ◽  
Impaired Insulin ◽  
Functional Features

Mitochondria associated membranes (MAM), which are the contact sites between endoplasmic reticulum (ER) and mitochondria, have emerged as an important hub for signaling molecules to integrate the cellular and organelle homeostasis, thus facilitating the adaptation of energy metabolism to nutrient status. This review explores the dynamic structural and functional features of the MAM and summarizes the various abnormalities leading to the impaired insulin sensitivity and metabolic diseases.

scholarly journals Growth control through regulation of insulin-signaling by nutrition-activated steroid hormone

2017 ◽  
Author(s):  
Kurt Buhler ◽  
Jason Clements ◽  
Mattias Winant ◽  
Veerle Vulsteke ◽  
Patrick Callaerts
Keyword(s):  
Insulin Signaling ◽  
Growth Regulation ◽  
Fat Body ◽  
Insulin Signalling ◽  
Steroid Hormone ◽  
Growth Control ◽  
Important Variable ◽  
Growth Defects ◽  
Insulin Producing Cells ◽  
Growth Promoting

AbstractGrowth and maturation are coordinated processes in all animals. Integration of internal cues, such as signalling pathways, with external cues such as nutritional status is paramount for an orderly progression of development in function of growth. In Drosophila, this coordination involves insulin and steroid signalling, but the mechanisms by which this occurs and how they are coordinated are incompletely understood. We show that production of the bioactive 20-hydroxyecdysone by the enzyme Shade in the fat body is a nutrient-dependent process. We demonstrate that during fed conditions, Shade plays a role in growth regulation, as knockdown of shade in the fat body resulted in growth defects and perturbed expression and release of the Drosophila insulin-like peptides from the insulin-producing cells (IPCs). We identify the trachea and IPCs as direct targets through which 20-hydroxyecdysone regulates insulin-signaling. The identification of the trachea-dependent regulation of insulin-signaling exposes an important variable that may have been overlooked in other studies focusing on insulin-signaling in Drosophila. Finally, we show with IPC-specific manipulations that 20E may both be a growth-promoting and growth-inhibiting signal in the IPCs acting through different nuclear receptors. Our findings provide a potentially conserved, novel mechanism by which nutrition can modulate steroid hormone bioactivation, reveal an important caveat of a commonly used transgenic tool to study IPC function and yield further insights as to how steroid and insulin signalling are coordinated during development to regulate growth and developmental timing.

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 Transcriptional Regulation of the Endoplasmic Reticulum Stress Gene Chop in Pancreatic Insulin-Producing Cells

Diabetes ◽  
2007 ◽  
Vol 56 (4) ◽  
pp. 1069-1077 ◽  
Author(s):  
P. Pirot ◽  
F. Ortis ◽  
M. Cnop ◽  
Y. Ma ◽  
L. M. Hendershot ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcriptional Regulation ◽  
Endoplasmic Reticulum Stress ◽  
Insulin Producing Cells ◽  
Pancreatic Insulin ◽  
Stress Gene

scholarly journals Proteostasis In The Endoplasmic Reticulum: Road to Cure

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1793 ◽  
Author(s):  
Nam ◽  
Jeon
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Protein Quality ◽  
Tumor Development ◽  
Therapeutic Interventions ◽  
Secretory Proteins ◽  
Unfolded Protein ◽  
Stress Signals ◽  
Protein Response

The endoplasmic reticulum (ER) is an interconnected organelle that is responsible for the biosynthesis, folding, maturation, stabilization, and trafficking of transmembrane and secretory proteins. Therefore, cells evolve protein quality-control equipment of the ER to ensure protein homeostasis, also termed proteostasis. However, disruption in the folding capacity of the ER caused by a large variety of pathophysiological insults leads to the accumulation of unfolded or misfolded proteins in this organelle, known as ER stress. Upon ER stress, unfolded protein response (UPR) of the ER is activated, integrates ER stress signals, and transduces the integrated signals to relive ER stress, thereby leading to the re-establishment of proteostasis. Intriguingly, severe and persistent ER stress and the subsequently sustained unfolded protein response (UPR) are closely associated with tumor development, angiogenesis, aggressiveness, immunosuppression, and therapeutic response of cancer. Additionally, the UPR interconnects various processes in and around the tumor microenvironment. Therefore, it has begun to be delineated that pharmacologically and genetically manipulating strategies directed to target the UPR of the ER might exhibit positive clinical outcome in cancer. In the present review, we summarize recent advances in our understanding of the UPR of the ER and the UPR of the ER–mitochondria interconnection. We also highlight new insights into how the UPR of the ER in response to pathophysiological perturbations is implicated in the pathogenesis of cancer. We provide the concept to target the UPR of the ER, eventually discussing the potential of therapeutic interventions for targeting the UPR of the ER for cancer treatment.

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