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https://www.readbyqxmd.com/read/28207290/fatty-acid-and-mineral-receptors-as-drug-targets-for-gastrointestinal-disorders
#1
Pawin Pongkorpsakol, Aekkacha Moonwiriyakit, Chatchai Muanprasat
Nutrient-sensing receptors, including fatty acid receptors (FFA1-FFA4), Ca(2+)-sensing receptors and Zn(2+)-sensing receptors, are involved in several biological processes. These receptors are abundantly expressed in the GI tract, where they have been shown to play crucial roles in regulating GI function. This review provides an overview of the GI functions of fatty acid and mineral receptors, including the regulation of gastric and enteroendocrine functions, GI motility, ion transport and cell growth. Recently, several lines of evidence have implicated these receptors as promising therapeutic targets for the treatment of GI disorders, for example, inflammatory bowel disease, colorectal cancer, metabolic syndrome and diarrheal diseases...
February 16, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28202725/stretchable-living-materials-and-devices-with-hydrogel-elastomer-hybrids-hosting-programmed-cells
#2
Xinyue Liu, Tzu-Chieh Tang, Eléonore Tham, Hyunwoo Yuk, Shaoting Lin, Timothy K Lu, Xuanhe Zhao
Living systems, such as bacteria, yeasts, and mammalian cells, can be genetically programmed with synthetic circuits that execute sensing, computing, memory, and response functions. Integrating these functional living components into materials and devices will provide powerful tools for scientific research and enable new technological applications. However, it has been a grand challenge to maintain the viability, functionality, and safety of living components in freestanding materials and devices, which frequently undergo deformations during applications...
February 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28202675/the-molecular-basis-of-mtorc1-regulated-translation
#3
REVIEW
Carson C Thoreen
The mammalian target of rapamycin (mTOR) signaling pathway is a master regulator of cell growth throughout eukaryotes. The pathway senses nutrient and other growth signals, and then orchestrates the complex systems of anabolic and catabolic metabolism that underpin the growth process. A central target of mTOR signaling is the translation machinery. mTOR uses a multitude of translation factors to drive the bulk production of protein that growth requires, but also to direct a post-transcriptional program of growth-specific gene expression...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28199315/szt2-dictates-gator-control-of-mtorc1-signalling
#4
Min Peng, Na Yin, Ming O Li
Mechanistic target of rapamycin complex 1 (TORC1) integrates nutrient signals to control cell growth and organismal homeostasis across eukaryotes. The evolutionarily conserved GATOR complex regulates mTORC1 signalling through Rag GTPases, and GATOR1 displays GTPase activating protein (GAP) activity for RAGA and RAGB (RAGA/B) and GATOR2 has been proposed to be an inhibitor of GATOR1. Furthermore, the metazoan-specific SESN proteins function as guanine nucleotide dissociation inhibitors (GDIs) for RAGA/B, and interact with GATOR2 with unknown effects...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28197911/the-roles-of-sumo-in-metabolic-regulation
#5
Elena Kamynina, Patrick J Stover
Protein modification with the small ubiquitin-related modifier (SUMO) can affect protein function, enzyme activity, protein-protein interactions, protein stability, protein targeting and cellular localization. SUMO influences the function and regulation of metabolic enzymes within pathways, and in some cases targets entire metabolic pathways by affecting the activity of transcription factors or by facilitating the translocation of entire metabolic pathways to subcellular compartments. SUMO modification is also a key component of nutrient- and metabolic-sensing mechanisms that regulate cellular metabolism...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28193602/preference-for-and-learning-of-amino-acids-in-larval-drosophila
#6
Nana Kudow, Daisuke Miura, Michael Schleyer, Naoko Toshima, Bertram Gerber, Teiichi Tanimura
Relative to other nutrients, less is known about how animals sense amino acids and how behaviour is organized accordingly. This is a significant gap in our knowledge, because amino acids are required for protein synthesis-and hence for life as we know it. Choosing larvae as a study case, we provide the first systematic analysis of both the preference behaviour for and the learning of all 20 canonical amino acids in Drosophila We report that preference for individual amino acids differs according to the kind of amino acid, both in first-instar and in third-instar larvae...
February 13, 2017: Biology Open
https://www.readbyqxmd.com/read/28185153/role-of-the-gut-on-glucose-homeostasis-lesson-learned-from-metabolic-surgery
#7
REVIEW
V Kamvissi-Lorenz, M Raffaelli, S Bornstein, G Mingrone
PURPOSE OF REVIEW: Bariatric surgery was initially intended to reduce weight, and only subsequently was the remission of type two diabetes (T2D) observed as a collateral event. At the moment, the term "metabolic surgery" is used to underline the fact that this type of surgery is performed specifically to treat diabetes and its metabolic complications, such as hyperlipidemia. RECENT FINDINGS: Randomized, controlled studies have recently supported the use of bariatric surgery, and in particular of Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) as an effective treatment for decompensated T2D...
February 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28183717/the-transcriptional-regulator-of-the-chaperone-response-hsf1-controls-hepatic-bioenergetics-and-protein-homeostasis
#8
Aijun Qiao, Xiongjie Jin, Junfeng Pang, Demetrius Moskophidis, Nahid F Mivechi
Metabolic energy reprogramming facilitates adaptations to a variety of stress conditions and cellular dysfunction, but how the energetic demands are monitored and met in response to physiological stimuli remains elusive. Our data support a model demonstrating that heat shock factor 1 (HSF1), a master transcriptional regulator of the chaperone response, has been coopted from its role as a critical protein quality-control regulator to having a central role in systemic energy sensing and for metabolic adaptation to nutrient availability...
February 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28180063/carnitine-acetyltransferase-crat-expression-in-macrophages-is-dispensable-for-nutrient-stress-sensing-and-inflammation
#9
Emily L Goldberg, Vishwa Deep Dixit
OBJECTIVE: Fatty acid oxidation in macrophages is thought to regulate inflammatory status and insulin-sensitivity. An important unanswered question in this field is whether carnitine acetyl-transferase (CrAT) that regulates fatty acid oxidation and mitochondrial acetyl-CoA balance is required to integrate nutrient stress sensing to inflammatory response in macrophages. METHODS: Mice with myeloid lineage-specific Crat deletion were subjected to several metabolic stressors, including high-fat diet-induced obesity, fasting, and LPS-induced endotoxemia...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28164071/transcriptional-coordination-of-hepatic-autophagy-by-nutrient-sensing-nuclear-receptor-ppar%C3%AE-and-fxr
#10
REVIEW
Jae Man Lee
Nuclear receptors are in general ligand-dependent transcription factors that control a variety of mammalian physiologies including development, differentiation, proliferation, and homeostasis. Recent studies have found that two nutrient-sensing nuclear receptors, peroxisome proliferator-activated receptor α and farnesoid x receptor, responding to fasting or feeding state, respectively are able to regulate autophagy, an evolutionarily conserved catabolic process involved in lysosomal degradation. In this review, we discuss the role of these nutrient-sensing nuclear receptors in an aspect of transcriptional regulation of autophagy, and how these nuclear receptor-driven transcriptional programs integrate lipophagy, a lipid autophagy with fatty acid oxidation to coordinate hepatic lipid metabolism in the fasted state of the liver...
December 2016: Annals of Pediatric Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28148462/exploration-of-phenylpropanoic-acids-as-agonists-of-the-free-fatty-acid-receptor-4-ffa4-identification-of-an-orally-efficacious-ffa4-agonist
#11
Steven M Sparks, Christopher Aquino, Pierette Banker, Jon L Collins, David Cowan, Caroline Diaz, Steven T Dock, Donald L Hertzog, Xi Liang, Erin D Swiger, Josephine Yuen, Grace Chen, Channa Jayawickreme, David Moncol, Christopher Nystrom, Vincent Rash, Thomas Rimele, Shane Roller, Sean Ross
The long chain free fatty acid receptor 4 (FFA4/GPR120) has recently been recognized as lipid sensor playing important roles in nutrient sensing and inflammation and thus holds potential as a therapeutic target for type 2 diabetes and metabolic syndrome. To explore the effects of stimulating this receptor in animal models of metabolic disease, we initiated work to identify agonists with appropriate pharmacokinetic properties to support progression into in vivo studies. Extensive SAR studies of a series of phenylpropanoic acids led to the identification of compound 29, a FFA4 agonist which lowers plasma glucose in two preclinical models of type 2 diabetes...
January 17, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28144629/pho4-is-essential-for-dissemination-of-cryptococcus-neoformans-to-the-host-brain-by-promoting-phosphate-uptake-and-growth-at-alkaline-ph
#12
Sophie Lev, Keren Kaufman-Francis, Desmarini Desmarini, Pierre G Juillard, Cecilia Li, Sebastian A Stifter, Carl G Feng, Tania C Sorrell, Georges E R Grau, Yong-Sun Bahn, Julianne T Djordjevic
Phosphate acquisition by fungi is regulated by the phosphate-sensing and acquisition (PHO) signaling pathway. Cryptococcus neoformans disseminates from the lung to the brain and is the commonest cause of fungal meningitis worldwide. To investigate the contribution of PHO signaling to cryptococcal dissemination, we characterized a transcription factor knockout strain (hlh3Δ/pho4Δ) defective in phosphate acquisition. Despite little similarity with other fungal Pho4 proteins, Hlh3/Pho4 functioned like a typical phosphate-responsive transcription factor in phosphate-deprived cryptococci, accumulating in nuclei and triggering expression of genes involved in phosphate acquisition...
January 2017: MSphere
https://www.readbyqxmd.com/read/28142198/incorporating-an-allosteric-regulatory-site-in-an-antibody-through-backbone-design
#13
Olga Khersonsky, Sarel J Fleishman
Allosteric regulation underlies living cells' ability to sense changes in nutrient and signaling-molecule concentrations, but the ability to computationally design allosteric regulation into non-allosteric proteins has been elusive. Allosteric-site design is complicated by the requirement to encode the relative stabilities of active and inactive conformations of the same protein in the presence and absence of both ligand and effector. To address this challenge, we used Rosetta to design the backbone of the flexible heavy-chain complementarity-determining region 3 (HCDR3), and used geometric matching and sequence optimization to place a Zn(2+) -coordination site in a fluorescein-binding antibody...
January 31, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28137482/epigallocatechin-3-gallate-egcg-activates-ampk-through-the-inhibition-of-glutamate-dehydrogenase-in-muscle-and-pancreatic-%C3%A3-cells-a-potential-beneficial-effect-in-the-pre-diabetic-state
#14
Shirin Pournourmohammadi, Mariagrazia Grimaldi, Malin H Stridh, Vanessa Lavallard, Helle S Waagepetersen, Claes B Wollheim, Pierre Maechler
Glucose homeostasis is determined by insulin secretion from the ß-cells in pancreatic islets and by glucose uptake in skeletal muscle and other insulin target tissues. While glutamate dehydrogenase (GDH) senses mitochondrial energy supply and regulates insulin secretion, its role in the muscle has not been elucidated. Here we investigated the possible interplay between GDH and the cytosolic energy sensing enzyme 5'-AMP kinase (AMPK), in both isolated islets and myotubes from mice and humans. The green tea polyphenol epigallocatechin-3-gallate (EGCG) was used to inhibit GDH...
January 27, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28135838/novel-role-of-the-mitochondrial-protein-fus1-in-protection-from-premature-hearing-loss-via-regulation-of-oxidative-stress-and-nutrient-and-energy-sensing-pathways-in-the-inner-ear
#15
Winston Tan, Lei Song, Morven Graham, Amy Schettino, Dhasakumar Navaratnam, Wendell G Yarbrough, Joseph Santos-Sacchi, Alla V Ivanova
AIMS: Acquired hearing loss is a worldwide epidemic that affects all ages. It is multifactorial in etiology with poorly characterized molecular mechanisms. Mitochondria are critical components in hearing. Here, we aimed to identify the mechanisms of mitochondria-dependent hearing loss using Fus1 KO mice, our novel model of mitochondrial dysfunction/oxidative stress. RESULTS: Using Auditory Brainstem Responses (ABRs) we characterized the Fus1 KO mouse as a novel, clinically relevant model of Age-Related Hearing Loss (ARHL) of metabolic etiology...
January 30, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28134810/acidosis-activates-endoplasmic-reticulum-stress-pathways-through-gpr4-in-human-vascular-endothelial-cells
#16
Lixue Dong, Elizabeth A Krewson, Li V Yang
Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the "Warburg effect"), and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined...
January 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28132818/salt-inducible-kinase-3-provides-sugar-tolerance-by-regulating-nadph-nadp-redox-balance
#17
Mari Teesalu, Bohdana M Rovenko, Ville Hietakangas
Nutrient-sensing pathways respond to changes in the levels of macronutrients, such as sugars, lipids, or amino acids, and regulate metabolic pathways to maintain organismal homeostasis [1, 2]. Consequently, nutrient sensing provides animals with the metabolic flexibility necessary for enduring temporal fluctuations in nutrient intake. Recent studies have shown that an animal's ability to survive on a high-sugar diet is determined by sugar-responsive gene regulation [3-8]. It remains to be elucidated whether other levels of metabolic control, such as post-translational regulation of metabolic enzymes, also contribute to organismal sugar tolerance...
February 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28128367/a-tachykinin-like-neuroendocrine-signalling-axis-couples-central-serotonin-action-and-nutrient-sensing-with-peripheral-lipid-metabolism
#18
Lavinia Palamiuc, Tallie Noble, Emily Witham, Harkaranveer Ratanpal, Megan Vaughan, Supriya Srinivasan
Serotonin, a central neuromodulator with ancient ties to feeding and metabolism, is a major driver of body fat loss. However, mechanisms by which central serotonin action leads to fat loss remain unknown. Here, we report that the FLP-7 neuropeptide and its cognate receptor, NPR-22, function as the ligand-receptor pair that defines the neuroendocrine axis of serotonergic body fat loss in Caenorhabditis elegans. FLP-7 is secreted as a neuroendocrine peptide in proportion to fluctuations in neural serotonin circuit functions, and its release is regulated from secretory neurons via the nutrient sensor AMPK...
January 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28127665/influence-of-nutrient-availability-and-quorum-sensing-on-the-formation-of-metabolically-inactive-microcolonies-within-structurally-heterogeneous-bacterial-biofilms-an-individual-based-3d-cellular-automata-model
#19
Lakshmi Machineni, Anil Rajapantul, Vandana Nandamuri, Parag D Pawar
The resistance of bacterial biofilms to antibiotic treatment has been attributed to the emergence of structurally heterogeneous microenvironments containing metabolically inactive cell populations. In this study, we use a three-dimensional individual-based cellular automata model to investigate the influence of nutrient availability and quorum sensing on microbial heterogeneity in growing biofilms. Mature biofilms exhibited at least three structurally distinct strata: a high-volume, homogeneous region sandwiched between two compact sections of high heterogeneity...
January 26, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28126903/the-significance-of-the-bifunctional-kinase-phosphatase-activities-of-ppip5ks-for-coupling-inositol-pyrophosphate-cell-signaling-to-cellular-phosphate-homeostasis
#20
Chunfang Gu, Hoai-Nghia Nguyen, Alexandre Hofer, Henning J Jessen, Xuming Dai, Huanchen Wang, Stephen B Shears
Proteins responsible for Pi homeostasis are critical for all life. In Saccharomyces cerevisiae, extracellular [Pi] is 'sensed' by the IP6K that synthesizes the intracellular inositol pyrophosphate, 5-InsP7, as follows: during a period of Pi-starvation, there is a decline in cellular [ATP]; the unusually low affinity of IP6Ks for ATP compels 5-InsP7 levels to fall in parallel (Wild et al., 2016, Science, 352:986). Hitherto, such Pi-sensing has not been documented in metazoans. Here, using a human intestinal epithelial cell line (HCT116), we show that levels of both 5-InsP7 and ATP decrease upon [Pi] starvation, and subsequently recover during Pi replenishment...
January 26, 2017: Journal of Biological Chemistry
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