دورية أكاديمية
MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis.
العنوان: | MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis. |
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المؤلفون: | Massey WJ; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Varadharajan V; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Banerjee R; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Brown AL; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Horak AJ; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Hohe RC; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Jung BM; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Qiu Y; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Chan ER; Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA., Pan C; Departments of Medicine, Microbiology, and Human Genetics, University of California Los Angeles, Los Angeles, CA, USA., Zhang R; Proteomics and Metabolomics Core, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Allende DS; Department of Anatomical Pathology, Cleveland Clinic, Cleveland, OH, USA., Willard B; Proteomics and Metabolomics Core, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Cheng F; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Lusis AJ; Departments of Medicine, Microbiology, and Human Genetics, University of California Los Angeles, Los Angeles, CA, USA., Brown JM; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: brownm5@ccf.org. |
المصدر: | Journal of lipid research [J Lipid Res] 2023 Apr; Vol. 64 (4), pp. 100349. Date of Electronic Publication: 2023 Feb 18. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0376606 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1539-7262 (Electronic) Linking ISSN: 00222275 NLM ISO Abbreviation: J Lipid Res Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: Memphis, Lipid Research, inc. |
مواضيع طبية MeSH: | Hyperinsulinism*/genetics , Hyperinsulinism*/metabolism , Insulin Resistance*/genetics , Non-alcoholic Fatty Liver Disease*/metabolism, Animals ; Mice ; Acylation ; Adipocytes/metabolism ; Arachidonic Acid/metabolism ; Diet, High-Fat/adverse effects ; Glucose/metabolism ; Homeostasis ; Mice, Inbred C57BL ; Mice, Knockout |
مستخلص: | We previously demonstrated that antisense oligonucleotide-mediated knockdown of Mboat7, the gene encoding membrane bound O-acyltransferase 7, in the liver and adipose tissue of mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance. Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression in mice but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. We generated Mboat7 floxed mice and created hepatocyte- and adipocyte-specific Mboat7 knockout mice using Cre-recombinase mice under the control of the albumin and adiponectin promoter, respectively. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. The expression of Mboat7 in white adipose tissue closely correlates with diet-induced obesity across a panel of ∼100 inbred strains of mice fed a high fat/high sucrose diet. Moreover, we found that adipocyte-specific genetic deletion of Mboat7 is sufficient to promote hyperinsulinemia, systemic insulin resistance, and mild fatty liver. Unlike in the liver, where Mboat7 plays a relatively minor role in maintaining arachidonic acid-containing PI pools, Mboat7 is the major source of arachidonic acid-containing PI pools in adipose tissue. Our data demonstrate that MBOAT7 is a critical regulator of adipose tissue PI homeostasis, and adipocyte MBOAT7-driven PI biosynthesis is closely linked to hyperinsulinemia and insulin resistance in mice. Competing Interests: Conflict of interest Dr. Daniela Allende reports serving as an Advisory Board Member for Incyte Corporation. All other authors declare no competing financial interests related to this work. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
معلومات مُعتمدة: | R01 DK120679 United States DK NIDDK NIH HHS; U01 AA026938 United States AA NIAAA NIH HHS; R01 HL144651 United States HL NHLBI NIH HHS; P01 HL147823 United States HL NHLBI NIH HHS; R01 HL148577 United States HL NHLBI NIH HHS; P30 DK020593 United States DK NIDDK NIH HHS; P50 AA024333 United States AA NIAAA NIH HHS; R01 HL130819 United States HL NHLBI NIH HHS; U24 DK059637 United States DK NIDDK NIH HHS; R01 DK130227 United States DK NIDDK NIH HHS; R01 DK117850 United States DK NIDDK NIH HHS |
فهرسة مساهمة: | Keywords: acyltransferase; arachidonic acid; diabetes; hepatocytes; hyperinsulinemia; metabolism; non-alcoholic fatty liver disease; obesity; phosphatidylinositol biosynthesis; systemic insulin resistance |
المشرفين على المادة: | 27YG812J1I (Arachidonic Acid) IY9XDZ35W2 (Glucose) 0 (lysophosphatidylinositol) EC 2.3.1- (Mboat7 protein, mouse) |
تواريخ الأحداث: | Date Created: 20230222 Date Completed: 20230426 Latest Revision: 20240509 |
رمز التحديث: | 20240509 |
مُعرف محوري في PubMed: | PMC10041558 |
DOI: | 10.1016/j.jlr.2023.100349 |
PMID: | 36806709 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1539-7262 |
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DOI: | 10.1016/j.jlr.2023.100349 |