DOCSLIB.ORG

Starvation Increases Insulin Sensitivity and Reduces Juvenile Hormone

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Starvation Increases Insulin Sensitivity and Reduces Juvenile Hormone Florida International University FIU Digital Commons Department of Biological Sciences College of Arts, Sciences & Education 1-29-2014 Starvation Increases Insulin Sensitivity and Reduces Juvenile Hormone Synthesis in Mosquitoes Meritxell Perez-Hedo Department of Biological Sciences, Florida International University, [email protected] Crisalejandra Rivera-Perez Department of Biological Sciences, Florida International University, [email protected] Fernando G. Noriega Department of Biological Sciences, Florida International University, [email protected] Follow this and additional works at: https://digitalcommons.fiu.edu/cas_bio Part of the Biology Commons Recommended Citation Perez-Hedo M, Rivera-Perez C, Noriega FG (2014) Starvation Increases Insulin Sensitivity and Reduces Juvenile Hormone Synthesis in Mosquitoes. PLoS ONE 9(1): e86183. doi:10.1371/journal.pone.0086183 This work is brought to you for free and open access by the College of Arts, Sciences & Education at FIU Digital Commons. It has been accepted for inclusion in Department of Biological Sciences by an authorized administrator of FIU Digital Commons. For more information, please contact [email protected]. Starvation Increases Insulin Sensitivity and Reduces Juvenile Hormone Synthesis in Mosquitoes Meritxell Perez-Hedo, Crisalejandra Rivera-Perez, Fernando G. Noriega* Department of Biological Sciences, Florida International University, Miami, Florida, United States of America Abstract Background: The interactions between the insulin signaling pathway (ISP) and juvenile hormone (JH) controlling reproductive trade-offs are well documented in insects. JH and insulin regulate reproductive output in mosquitoes; both hormones are involved in a complex regulatory network, in which they influence each other and in which the mosquito’s nutritional status is a crucial determinant of the network’s output. Previous studies reported that the insulin-TOR (target of rapamacyn) signaling pathway is involved in the nutritional regulation of JH synthesis in female mosquitoes. The present studies further investigate the regulatory circuitry that controls both JH synthesis and reproductive output in response to nutrient availability. Methods: We used a combination of diet restriction, RNA interference (RNAi) and insulin treatments to modify insulin signaling and study the cross-talk between insulin and JH in response to starvation. JH synthesis was analyzed using a newly developed assay utilizing fluorescent tags. Conclusions: Our results reveal that starvation decreased JH synthesis via a decrease in insulin signaling in the corpora allata (CA). Paradoxically, starvation-induced up regulation of insulin receptor transcripts and therefore ‘‘primed’’ the gland to respond rapidly to increases in insulin levels. During this response to starvation the synthetic potential of the CA remained unaffected, and the gland rapidly and efficiently responded to insulin stimulation by increasing JH synthesis to rates similar to those of CA from non-starved females. Citation: Perez-Hedo M, Rivera-Perez C, Noriega FG (2014) Starvation Increases Insulin Sensitivity and Reduces Juvenile Hormone Synthesis in Mosquitoes. PLoS ONE 9(1): e86183. doi:10.1371/journal.pone.0086183 Editor: Immo A. Hansen, New Mexico State University, United States of America Received October 31, 2013; Accepted December 5, 2013; Published January 29, 2014 Copyright: ß 2014 Perez-Hedo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by National Institutes of Health (NIH) grant AI 45545 to FGN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected] Introduction response to a positive nutritional status, tends to stimulate egg production in mosquitoes [10]. The correct allocation of nutrients between conflicting needs How these two hormonal signaling pathways (ISP and JH) such as reproduction, growth, maturation or flight is a vital interact to regulate all the physiological functions necessary for egg component of an insect’s life-history strategy [1]. Juvenile production is not totally clear. JH titers in female adult mosquitoes hormone (JH) is a remarkably versatile molecule with major are mainly determined by the rate at which the corpora allata (CA) effects on various aspects of development and life history in insects, synthesize JH [11]. Changes in JH synthesis in female adult A. including metamorphosis, behavior, reproduction, diapause, stress aegypti mosquito are very dynamic and nutrition-dependent [12]. resistance and aging [2]. The insulin signaling pathways (ISP) is an Previous studies reported that the insulin/target of rapamaycin evolutionary conserved systemic nutritional sensor that plays a (TOR) pathway is involved in the nutritional regulation of JH central role in the transduction of nutritional signals that regulate synthesis in female mosquitoes [13]. Application of bovine insulin cell growth and metabolism [3,4]. JH and insulin are involved in a on the mosquito CA-CC incubated in vitro caused a strong and fast complex regulatory network, in which they influence each other stimulation on JH synthesis; while systemic depletion of TOR by and in which the insect’s nutritional status is a crucial determinant RNAi and rapamycin administration had inhibitory effects on JH of the network’s output [5]. synthesis [13]. In addition, reducing insulin signaling with PI3K The reproductive cycle of female mosquitoes proceeds through inhibitors rapidly reduced JH biosynthetic enzyme transcripts; a previtellogenic stage (PVGS), an ovarian resting stage (ORS) and validating that a transcriptional regulation of the genes encoding a vitellogenic stage (VGS) [6]. In Aedes aegypti JH is a key mediator JH biosynthetic enzymes is at least partially responsible for the of trade-offs between survival and reproduction during the PVGS dynamic changes of JH biosynthesis in mosquitoes [13]. and ORS [7,8]. Regardless of the nutritional status of a female Here diet restriction, in vivo depletion of INSr and FOXO using mosquito, topical application of JH will override other signaling RNA interference (RNAi) and insulin treatments were used to pathways and stimulate oogenesis even in isolated abdomens [9,7]. modify insulin signaling and study the cross-talk between insulin In addition, increased insulin production and signaling, in and JH in response to starvation. Our results reveal that starvation PLOS ONE | www.plosone.org 1 January 2014 | Volume 9 | Issue 1 | e86183 Insulin and JH decreased JH synthesis via a decrease in insulin signaling in the To obtain absolute transcript values, standard curves were made CA. Starvation-induced up regulation of the insulin receptor from serial dilutions of plasmids containing the mosquito genes increased CA insulin sensitivity and might ‘‘prime’’ the gland to (300,000; 30,000; 3,000; 300; 30 copies of a plasmid per reaction). respond rapidly to increases in insulin levels after feeding Real-time data were collected by the 7300 System SDS Software resumption. During this response to starvation the synthetic and analyzed in Microsoft Excel. Transcript levels were normal- potential of the CA remained unaffected, and the gland rapidly ized with rpL32 transcript levels in the same sample. Each qPCR and efficiently responded to insulin stimulation by increasing JH data point is the average of 4 to 6 independent experiments synthesis to rates similar to those of CA from non-starved females. analyzing either three groups of ten CA or three thoraxes. The primer probes sequences and accession numbers for the genes Materials and Methods studied, insulin receptor (INSr), Forkhead-box-binding protein (FOXO), target of rapamycin (TOR), translation initiation Insects inhibitor eIF4E-binding protein (4E-BP) and juvenile hormone Aedes aegypti of the Rockefeller strain were reared at 28uC and acid methyltransferase (JHAMT); as well as the housekeeping gene 80% relative humidity under a photoperiod of 16 h light: 8 h dark. 60S ribosomal protein L32 are included in Table S1. Female were offered a cotton pad soaked in 20% sucrose solution for the first 24 h after adult emergence. Afterwards, one day-old RNA interference females were separated into two experimental groups: starved Synthesis and microinjections of double-stranded RNA females were offered water, and sugar-fed females were main- (dsRNA) were performed as described by Perez-Hedo et al. [13]. tained on a 20% sucrose solution. All experiments were performed INSr, FOXO and YFP (yellow fluorescent protein) target with 4-day old virgin females. sequences for dsRNA synthesis were amplified by PCR using the To test the effect of starvation we used four days old females INSri, FOXOi and YFPi primers (Table S1). The resulting because our RNAi protocol requires waiting a 4-day period after amplicons were diluted 50-fold, and 1 ml of these diluted injection to be effective [13]. Starving newly emerged females for 4 amplicons were used as template in PCR reactions with primers days resulted in an elevated mortality. Feeding females on a high containing T7 promoter sequences (INSri _T7, FOXOi _T7 and sugar meal (20% sucrose) for 24 h before starving them for 3 days YFPi_T7) (Table
Load more

Recommended publications
  • Global Proteomics Analysis of the Response to Starvation in C. Elegans*DS
    Research Author’s Choice © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. This paper is available on line at http://www.mcponline.org Global Proteomics Analysis of the Response to Starvation in C. elegans*□S Mark Larance‡¶, Ehsan Pourkarimi‡¶, Bin Wang‡, Alejandro Brenes Murillo, Robert Kent, Angus I. Lamond‡§, and Anton Gartner‡§ Periodic starvation of animals induces large shifts in me- ment, however, requires feeding and progresses through four tabolism but may also influence many other cellular sys- developmental stages (L1-L4). The effect of starvation varies tems and can lead to adaption to prolonged starvation at these different developmental stages. Hatching of L1 stage conditions. To date, there is limited understanding of larvae in the absence of food leads to a starvation response how starvation affects gene expression, particularly at without overt morphogenesis that allows for ϳ2 weeks of the protein level. Here, we have used mass-spectro- survival (2). Mid- and late-stage L4 larvae, upon starvation, metry-based quantitative proteomics to identify global develop into adults but preserve resources by reducing germ changes in the Caenorhabditis elegans proteome due to cell proliferation and thereby holding a limited number of acute starvation of young adult animals. Measuring changes in the abundance of over 5,000 proteins, we embryos (3, 4). show that acute starvation rapidly alters the levels of Conserved genetic pathways have been identified that link hundreds of proteins, many involved in central metabolic nutrient availability to metabolic remodeling, stress resistance pathways, highlighting key regulatory responses. Surpris- pathways, and enhanced life span. Many of these pathways ingly, we also detect changes in the abundance of chro- overlap and include TOR, AMPK, autophagy, and insulin/ matin-associated proteins, including specific linker his- IGF-1 signaling.
    [Show full text]
  • Transcriptomic Analysis Reveals Niche Gene Expression Effects of Beta
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.19.427259; this version posted January 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Transcriptomic analysis reveals niche gene expression effects of beta- hydroxybutyrate in primary myotubes Philip M. M. Ruppert1, Guido J. E. J. Hooiveld1, Roland W. J. Hangelbroek1,2, Anja Zeigerer3,4, Sander Kersten1,$ 1Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands; 2Euretos B.V., Utrecht, The Netherlands 3Institute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, Germany, Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany; 4German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany $ To whom correspondence should be addressed: Sander Kersten, PhD Division of Human Nutrition and Health Wageningen University Stippeneng 4 6708 WE Wageningen The Netherlands Phone: +31 317 485787 Email: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2021.01.19.427259; this version posted January 20, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abbreviations: βOHB β-hydroxybutyrate AcAc acetoacetate Kbhb lysine β-hydroxybutyrylation HDAC histone deacetylase bioRxiv preprint doi: https://doi.org/10.1101/2021.01.19.427259; this version posted January 20, 2021.
    [Show full text]
  • A Glucose-Starvation Response Regulates the Diffusion of Macromolecules Ryan P
    A glucose-starvation response regulates the diffusion of macromolecules Ryan P. Joyner, Jeffrey H. Tang, Jonne Helenius, Elisa Dultz, Christiane Brune, Liam J. Holt, Sébastien Huet, Daniel J. Müller, Karsten Weis To cite this version: Ryan P. Joyner, Jeffrey H. Tang, Jonne Helenius, Elisa Dultz, Christiane Brune, et al.. Aglucose- starvation response regulates the diffusion of macromolecules. eLife, eLife Sciences Publication, 2016, 5, pp.e09376. 10.7554/eLife.09376. hal-01295659 HAL Id: hal-01295659 https://hal-univ-rennes1.archives-ouvertes.fr/hal-01295659 Submitted on 4 Oct 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. RESEARCH ARTICLE A glucose-starvation response regulates the diffusion of macromolecules Ryan P Joyner1, Jeffrey H Tang2, Jonne Helenius3, Elisa Dultz1†, Christiane Brune1, Liam J Holt4, Sebastien Huet5, Daniel J Mu¨ ller3, Karsten Weis1,2* 1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; 2Institute of Biochemistry, Department of Biology, ETH Zurich, Zu¨ rich, Switzerland; 3Department of Biosystems Science and Engineering, ETH Zurich, Zu¨ rich, Switzerland; 4Institute for Systems Genetics, New York University School of Medicine, New York, United States; 5CNRS, UMR 6290, Institut Ge´ne´tique et De´veloppement, University of Rennes, Rennes, France Abstract The organization and biophysical properties of the cytosol implicitly govern molecular interactions within cells.
    [Show full text]
  • Nutrient Limitation Inactivates Mrc1-To-Cds1 Checkpoint Signalling in Schizosaccharomyces Pombe
    cells Article Nutrient Limitation Inactivates Mrc1-to-Cds1 Checkpoint Signalling in Schizosaccharomyces pombe Jessica Fletcher 1,2 ID , Liam Griffiths 1 and Thomas Caspari 1,3,* ID 1 School of Medical Sciences, Bangor University, Bangor LL57 2UW, UK; j.f.fl[email protected] (J.F.); lbgriffi[email protected] (L.G.) 2 Medical School, Swansea University, Swansea SA2 8PP, UK 3 Postgraduate Doctoral Studies, Paracelsus Medical University, 5020 Salzburg, Austria * Correspondence: [email protected]; Tel.: +43-662-2420-80245 Received: 11 February 2018; Accepted: 21 February 2018; Published: 23 February 2018 Abstract: The S. pombe checkpoint kinase, Cds1, protects the integrity of stalled DNA replication forks after its phosphorylation at threonine-11 by Rad3 (ATR). Modified Cds1 associates through its N-terminal forkhead-associated domain (FHA)-domain with Mrc1 (Claspin) at stalled forks. We report here that nutrient starvation results in post-translational changes to Cds1 and the loss of Mrc1. A drop in glucose after a down-shift from 3% to 0.1–0.3%, or when cells enter the stationary phase, triggers a sharp decline in Mrc1 and the accumulation of insoluble Cds1. Before this transition, Cds1 is transiently activated and phosphorylated by Rad3 when glucose levels fall. Because this coincides with the phosphorylation of histone 2AX at S129 by Rad3, an event that occurs towards the end of every unperturbed S phase, we suggest that a glucose limitation promotes the exit from the S phase. Since nitrogen starvation also depletes Mrc1 while Cds1 is post-translationally modified, we suggest that nutrient limitation is the general signal that promotes exit from S phase before it inactivates the Mrc1–Cds1 signalling component.
    [Show full text]
  • Limitation of Phosphate Assimilation Maintains Cytoplasmic
    bioRxiv preprint doi: https://doi.org/10.1101/2020.09.05.284430; this version posted September 5, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 1 Limitation of phosphate assimilation maintains cytoplasmic 2 magnesium homeostasis 3 4 Roberto E. Bruna1,2, Christopher G. Kendra1,2, Eduardo A. Groisman3,4, Mauricio 5 H. Pontes1,2* 6 7 1 Department of Pathology and Laboratory Medicine, and 2 Department of Microbiology 8 and Immunology, Penn State College of Medicine, 500 University Drive, P.O. Box 9 17033, Hershey, PA, 17033, USA 10 3 Department of Microbial Pathogenesis, Yale School of Medicine, 295 Congress 11 Avenue, New Haven, CT 06536, USA 12 4 Yale Microbial Sciences Institute, P.O. Box 27389, West Haven, CT, 06516, USA 13 14 *Address correspondence to Mauricio H. Pontes, 15 [email protected] 16 17 Classification 18 Biology, Microbiology 19 20 Keywords 21 Phosphate, ATP, Magnesium, MgtC, Salmonella 22 23 24 bioRxiv preprint doi: https://doi.org/10.1101/2020.09.05.284430; this version posted September 5, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 25 Author Contributions 26 R.E.B., C.G.K., E.A.G. and M.H.P.
    [Show full text]
  • Role of the Evolutionarily Conserved Starvation Response in Anorexia
    Molecular Psychiatry (2011) 16, 595–603 & 2011 Macmillan Publishers Limited All rights reserved 1359-4184/11 www.nature.com/mp FEATURE REVIEW Role of the evolutionarily conserved starvation response in anorexia nervosa DS Dwyer1,2, RY Horton1 and EJ Aamodt3 1Department of Psychiatry, LSU Health Sciences Center, Shreveport, LA, USA; 2Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center, Shreveport, LA, USA and 3Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, Shreveport, LA, USA This review will summarize recent findings concerning the biological regulation of starvation as it relates to anorexia nervosa (AN), a serious eating disorder that mainly affects female adolescents and young adults. AN is generally viewed as a psychosomatic disorder mediated by obsessive concerns about weight, perfectionism and an overwhelming desire to be thin. By contrast, the thesis that will be developed here is that, AN is primarily a metabolic disorder caused by defective regulation of the starvation response, which leads to ambivalence towards food, decreased food consumption and characteristic psychopathology. We will trace the starvation response from yeast to man and describe the central role of insulin (and insulin-like growth factor-1 (IGF-1))/Akt/ F-box transcription factor (FOXO) signaling in this response. Akt is a serine/threonine kinase downstream of the insulin and IGF-1 receptors, whereas FOXO refers to the subfamily of Forkhead box O transcription factors, which are regulated by Akt. We will also discuss how initial bouts of caloric restriction may alter the production of neurotransmitters that regulate appetite and food-seeking behavior and thus, set in motion a vicious cycle.
    [Show full text]
  • Survival of Starving Yeast Is Correlated with Oxidative Stress Response And
    Survival of starving yeast is correlated with oxidative PNAS PLUS stress response and nonrespiratory mitochondrial function Allegra A. Pettia,b, Christopher A. Crutchfielda,c, Joshua D. Rabinowitza,c, and David Botsteina,b,1 aLewis-Sigler Institute for Integrative Genomics and Departments of bMolecular Biology and cChemistry, Princeton University, Princeton, NJ 08544 Edited by Jasper Rine, University of California, Berkeley, CA, and approved June 8, 2011 (received for review January 31, 2011) Survival of yeast during starvation has been shown to depend on tions for other areas of biology, because connections among the the nature of the missing nutrient(s). In general, starvation for same processes that are influenced by nutrient starvation have “natural” nutrients such as sources of carbon, phosphate, nitro- been documented in cancer, aging, and the yeast metabolic cycle. gen, or sulfate results in low death rates, whereas starvation for As a first step toward understanding general determinants of amino acids or other metabolites in auxotrophic mutants results in starvation phenotype, we sought to identify transcriptional cor- rapid loss of viability. Here we characterized phenotype, gene ex- relates of “successful” or “survivable” starvation—that is, starva- pression, and metabolite abundance during starvation for methi- tion that leads to concerted cell cycle arrest, glucose conservation, onine. Some methionine auxotrophs (those with blocks in the and, most importantly, survival. To this end, we compared the biosynthetic pathway) respond to methionine starvation like yeast physiology and gene expression of S. cerevisiae in response to starving for natural nutrients such as phosphate or sulfate: they starvation for a variety of previously characterized nutrients, and undergo a uniform cell cycle arrest, conserve glucose, and survive.
    [Show full text]
  • Daf-16/Foxo Promotes Gluconeogenesis and Trehalose
    RESEARCH ARTICLE daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival Jonathan D Hibshman1,2, Alexander E Doan1, Brad T Moore1, Rebecca EW Kaplan1,2, Anthony Hung1, Amy K Webster1,2, Dhaval P Bhatt3, Rojin Chitrakar1, Matthew D Hirschey3,4,5, L Ryan Baugh1,2* 1Department of Biology, Duke University, Durham, United States; 2University Program in Genetics and Genomics, Duke University, Durham, United States; 3Duke Molecular Physiology Institute, Duke University, Durham, United States; 4Department of Medicine, Duke University, Durham, United States; 5Department of Pharmacology & Cancer Biology, Duke University, Durham, United States Abstract daf-16/FoxO is required to survive starvation in Caenorhabditis elegans, but how daf- 16IFoxO promotes starvation resistance is unclear. We show that daf-16/FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16/FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant. DOI: https://doi.org/10.7554/eLife.30057.001 *For correspondence: [email protected] Competing interests: The Introduction authors declare that no Nutrient availability naturally fluctuates, and animals have a variety of physiological responses that competing interests exist.
    [Show full text]
  • FGF21 and the Late Adaptive Response to Starvation in Humans
    The Journal of Clinical Investigation RESEARCH ARTICLE FGF21 and the late adaptive response to starvation in humans Pouneh K. Fazeli,1,2 Mingyue Lun,3 Soo M. Kim,3 Miriam A. Bredella,2,4 Spenser Wright,1 Yang Zhang,3 Hang Lee,2,5 Ciprian Catana,2,6 Anne Klibanski,1,2 Parth Patwari,7 and Matthew L. Steinhauser2,3,7 1Department of Medicine, Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA. 2Harvard Medical School, Boston, Massachusetts, USA. 3Department of Medicine, Division of Genetics, Brigham and Women’s Hospital, Boston, Massachusetts, USA. 4Department of Radiology and 5Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, USA. 7Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA. In mice, FGF21 is rapidly induced by fasting, mediates critical aspects of the adaptive starvation response, and displays a number of positive metabolic properties when administered pharmacologically. In humans, however, fasting does not consistently increase FGF21, suggesting a possible evolutionary divergence in FGF21 function. Moreover, many key aspects of FGF21 function in mice have been identified in the context of transgenic overexpression or administration of supraphysiologic doses, rather than in a physiologic setting. Here, we explored the dynamics and function of FGF21 in human volunteers during a 10-day fast. Unlike mice, which show an increase in circulating FGF21 after only 6 hours, human subjects did not have a notable surge in FGF21 until 7 to 10 days of fasting. Moreover, we determined that FGF21 induction was associated with decreased thermogenesis and adiponectin, an observation that directly contrasts with previous reports based on supraphysiologic dosing.
    [Show full text]
  • Transcriptome Analysis Provides Insights Into the Root Response of Chinese Fir to Phosphorus Defciency
    Transcriptome Analysis Provides Insights into the Root Response of Chinese Fir to Phosphorus Deciency Wanting Chen Forestry College, Fujian Agriculture and Forestry University Mengyan Zhou Forestry College, Fujian Agriculture and Forestry University Mingzhen Zhao Forestry College, Fujian Agriculture and Forestry University Ranhong Chen Forestry College, Fujian Agriculture and Forestry University Mulualem Tigabu Forestry College, Fujian Agriculture and Forestry University Pengfei Wu Forestry College, Fujian Agriculture and Forestry University Ming Li ( [email protected] ) Forestry College, Fujian Agriculture and Forestry University Xiangqing Ma Forestry College, Fujian Agriculture and Forestry University Research Article Keywords: Cunninghamia lanceolate, phosphorus deciency, transcriptome, differential expression genes, citric acid and glyoxylate cycle pathway Posted Date: April 9th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-400319/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/28 Abstract Background: Phosphorus is one of the essential elements for plant growth and development, but the content of plant available phosphorus (Pi) in many soil types is low. As a fast-growing timber species, Chinese r is in great demand of Pi, and the lack of Pi in soil restricts the increase of productivity of Chinese r plantation. Root morphology and the synthesis and secretion of organic acids play an important role in the uptake of phosphorus, but the molecular mechanisms of Chinese r in response to Pi deciency are largely unexplored. Results: In this study, seedlings of Yang 061 clone were grown under three Pi supply levels (0, 5 and 10 mg·L-1 P) and morphological attributes, organic acid content and enzyme activity were measured, the transcriptome data of Chinese r root system were obtained and the expression levels of phosphorus responsive genes and organic acid synthesis related genes on citric acid and glyoxylate cycle pathway were determined.
    [Show full text]
  • Lipid Catabolism in Starved Yak Is Inhibited by Intravenous Infusion of Β-Hydroxybutyrate
    animals Article Lipid Catabolism in Starved Yak Is Inhibited by Intravenous Infusion of β-Hydroxybutyrate Huawei Zou 1, Rui Hu 1, Xianwen Dong 1, Ali Mujtaba Shah 1,2 , Zhisheng Wang 1,*, Jian Ma 1 , Quanhui Peng 1, Bai Xue 1, Lizhi Wang 1 , Xiangfei Zhang 1 , Shaoyu Zeng 1, Xueying Wang 1, Junhua Shi 1 and Fengpeng Li 1 1 “Low Carbon Breeding Cattle and Safety Production” University Key Laboratory of Sichuan Province, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 61130, China; [email protected] (H.Z.); [email protected] (R.H.); [email protected] (X.D.); [email protected] (A.M.S.); [email protected] (J.M.); [email protected] (Q.P.); [email protected] (B.X.); [email protected] (L.W.); [email protected] (X.Z.); [email protected] (S.Z.); [email protected] (X.W.); [email protected] (J.S.); [email protected] (F.L.) 2 Department of Livestock Production, Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand 67210, Pakistan * Correspondence: [email protected] Received: 6 December 2019; Accepted: 11 January 2020; Published: 15 January 2020 Simple Summary: Yak, which is the predominant and semi-domesticated livestock on the Qinghai-Tibet Plateau, suffers severe starvation and body weight reduction in the cold season because of the harsh highland environment. Lipids are important energy sources to starvation animals. β-hydroxybutyrate (BHBA) that is derived from lipid decomposition as the primary ketone body is with the function not only to provide energy for animals as energy materials, but also regulate lipid metabolism as signaling molecular.
    [Show full text]
  • FGF21—Central Pathways of Action Unravelled
    RESEARCH HIGHLIGHTS Nature Reviews Endocrinology 9, 563 (2013); published online 27 August 2013; doi:10.1038/nrendo.2013.168 NEUROENDOCRINOLOGY FGF21—central pathways of action unravelled wo new studies published in Nature β-klotho was selectively eliminated in the Medicine implicate the central SCN and DVC but not in other tissues), Tnervous system in the mechanisms to study the biological consequences of of action by which fibroblast growth chronic FGF21 exposure or of eliminating factor 21 (FGF21) exerts its effects central FGF21 action, respectively. on metabolism and growth in mice. To examine the effects of FGF21 on Furthermore, the data reveal hitherto circadian rhythm, Kliewer and colleagues unknown actions of centrally acting performed wheel-running experiments. FGF21: the induction of glucocorticoid “These experiments were the logical next levels, the inhibition of female ovulation, step once we found β-klotho in the SCN, and the alteration of circadian behaviour. the master regulator of circadian rhythm,” The hepatokine FGF21 has important explains Kliewer. roles in energy metabolism. For example, The studies showed that “many if FGF21 is well-known to induce metabolic not most of FGF21’s biological actions © iStockphoto/Thinkstock processes in response to starvation, such require it to act on the brain,” as Kliewer to long-term fasting, FGF21 is released as increased ketogenesis and inhibition describes it. Previously established from the liver and circulates to the brain, of growth. Direct effects of FGF21 on effects of FGF21—that is, the induction where it acts to regulate diverse aspects of peripheral target tissues, such as white of metabolic processes such as increased the adaptive starvation response in other adipose tissue, have previously been fatty acid oxidation, reduced insulin levels tissues,” comments Kliewer.
    [Show full text]