MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis
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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227523000226 |
| _version_ | 1827963129617711104 |
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| author | William J. Massey Venkateshwari Varadharajan Rakhee Banerjee Amanda L. Brown Anthony J. Horak Rachel C. Hohe Bryan M. Jung Yunguang Qiu E. Ricky Chan Calvin Pan Renliang Zhang Daniela S. Allende Belinda Willard Feixiong Cheng Aldons J. Lusis J. Mark Brown |
| author_facet | William J. Massey Venkateshwari Varadharajan Rakhee Banerjee Amanda L. Brown Anthony J. Horak Rachel C. Hohe Bryan M. Jung Yunguang Qiu E. Ricky Chan Calvin Pan Renliang Zhang Daniela S. Allende Belinda Willard Feixiong Cheng Aldons J. Lusis J. Mark Brown |
| author_sort | William J. Massey |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T16:54:40Z |
| format | Article |
| id | doaj.art-4c86927b018244dab52502931112ad14 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-09T16:54:40Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-4c86927b018244dab52502931112ad142023-04-21T06:40:37ZengElsevierJournal of Lipid Research0022-22752023-04-01644100349MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasisWilliam J. Massey0Venkateshwari Varadharajan1Rakhee Banerjee2Amanda L. Brown3Anthony J. Horak4Rachel C. Hohe5Bryan M. Jung6Yunguang Qiu7E. Ricky Chan8Calvin Pan9Renliang Zhang10Daniela S. Allende11Belinda Willard12Feixiong Cheng13Aldons J. Lusis14J. Mark Brown15Department 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, USADepartment 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, USADepartment 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, USADepartment 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, USADepartment 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, USADepartment 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, USADepartment 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, USAGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USAInstitute for Computational Biology, Case Western Reserve University, Cleveland, OH, USADepartments of Medicine, Microbiology, and Human Genetics, University of California Los Angeles, Los Angeles, CA, USAProteomics and Metabolomics Core, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USADepartment of Anatomical Pathology, Cleveland Clinic, Cleveland, OH, USAProteomics and Metabolomics Core, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USAGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USADepartments of Medicine, Microbiology, and Human Genetics, University of California Los Angeles, Los Angeles, CA, USADepartment 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; For correspondence: J. Mark BrownWe 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.http://www.sciencedirect.com/science/article/pii/S0022227523000226non-alcoholic fatty liver diseaseobesitymetabolismdiabeteshyperinsulinemiasystemic insulin resistance |
| spellingShingle | William J. Massey Venkateshwari Varadharajan Rakhee Banerjee Amanda L. Brown Anthony J. Horak Rachel C. Hohe Bryan M. Jung Yunguang Qiu E. Ricky Chan Calvin Pan Renliang Zhang Daniela S. Allende Belinda Willard Feixiong Cheng Aldons J. Lusis J. Mark Brown MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis Journal of Lipid Research non-alcoholic fatty liver disease obesity metabolism diabetes hyperinsulinemia systemic insulin resistance |
| title | MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis |
| title_full | MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis |
| title_fullStr | MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis |
| title_full_unstemmed | MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis |
| title_short | MBOAT7-driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis |
| title_sort | mboat7 driven lysophosphatidylinositol acylation in adipocytes contributes to systemic glucose homeostasis |
| topic | non-alcoholic fatty liver disease obesity metabolism diabetes hyperinsulinemia systemic insulin resistance |
| url | http://www.sciencedirect.com/science/article/pii/S0022227523000226 |
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