Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice

Summary: Angiopoietin-like protein 8 (Angptl8), expressed in the liver and adipocytes, forms a complex with Angptl3 or Angptl4, which regulates lipoprotein lipase and triglyceride metabolism. However, the precise functions of adipocyte Angptl8 remain elusive. Here we report that adipocyte-specific i...

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Main Authors: Anindya Ghosh, Isabelle Chénier, Yat Hei Leung, Abel K. Oppong, Marie-Line Peyot, S. R. Murthy Madiraju, Irina Al-Khairi, Jehad Abubaker, Fahd Al-Mulla, Marc Prentki, Mohamed Abu-Farha
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224025173
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author Anindya Ghosh
Isabelle Chénier
Yat Hei Leung
Abel K. Oppong
Marie-Line Peyot
S. R. Murthy Madiraju
Irina Al-Khairi
Jehad Abubaker
Fahd Al-Mulla
Marc Prentki
Mohamed Abu-Farha
author_facet Anindya Ghosh
Isabelle Chénier
Yat Hei Leung
Abel K. Oppong
Marie-Line Peyot
S. R. Murthy Madiraju
Irina Al-Khairi
Jehad Abubaker
Fahd Al-Mulla
Marc Prentki
Mohamed Abu-Farha
author_sort Anindya Ghosh
collection DOAJ
description Summary: Angiopoietin-like protein 8 (Angptl8), expressed in the liver and adipocytes, forms a complex with Angptl3 or Angptl4, which regulates lipoprotein lipase and triglyceride metabolism. However, the precise functions of adipocyte Angptl8 remain elusive. Here we report that adipocyte-specific inducible Angptl8-knockout (AT-A8-KO) male mice on normal diet showed minor phenotypic changes, but after a high-fat high fructose (HFHF) diet, exhibited decreased body weight gain and glycemia, elevated rectal temperature and early dark phase energy expenditure compared to the Cre controls. AT-A8-KO mice also displayed improved glucose tolerance, a trend for better insulin sensitivity, improved insulin-stimulated glucose uptake in adipose tissues, and reduced visceral adipose tissue crown-like structures, plasma MCP-1 and leptin levels. The results indicate the importance of adipose Angptl8 in the context of nutri-stress and obesity, as its deletion in mice promotes a metabolically healthy obese phenotype by slightly ameliorating obesity, improving glucose and energy homeostasis, and mitigating inflammation.
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spelling doaj-art-050289fe5d4542d5980451a7aff949a32025-08-20T02:39:48ZengElsevieriScience2589-00422024-12-01271211129210.1016/j.isci.2024.111292Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in miceAnindya Ghosh0Isabelle Chénier1Yat Hei Leung2Abel K. Oppong3Marie-Line Peyot4S. R. Murthy Madiraju5Irina Al-Khairi6Jehad Abubaker7Fahd Al-Mulla8Marc Prentki9Mohamed Abu-Farha10Departments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, CanadaDepartments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, CanadaDepartments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, CanadaDepartments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, CanadaDepartments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, CanadaDepartments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, CanadaBiochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, KuwaitBiochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, KuwaitTranslational Research Department, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartments of Nutrition, Biochemistry and Molecular Medicine, University of Montreal, and Montreal Diabetes Research Center, Centre de Recherche Du Centre Hospitalier de L’Université de Montréal (CRCHUM), Montréal, QC, Canada; Corresponding authorBiochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; Translational Research Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; Corresponding authorSummary: Angiopoietin-like protein 8 (Angptl8), expressed in the liver and adipocytes, forms a complex with Angptl3 or Angptl4, which regulates lipoprotein lipase and triglyceride metabolism. However, the precise functions of adipocyte Angptl8 remain elusive. Here we report that adipocyte-specific inducible Angptl8-knockout (AT-A8-KO) male mice on normal diet showed minor phenotypic changes, but after a high-fat high fructose (HFHF) diet, exhibited decreased body weight gain and glycemia, elevated rectal temperature and early dark phase energy expenditure compared to the Cre controls. AT-A8-KO mice also displayed improved glucose tolerance, a trend for better insulin sensitivity, improved insulin-stimulated glucose uptake in adipose tissues, and reduced visceral adipose tissue crown-like structures, plasma MCP-1 and leptin levels. The results indicate the importance of adipose Angptl8 in the context of nutri-stress and obesity, as its deletion in mice promotes a metabolically healthy obese phenotype by slightly ameliorating obesity, improving glucose and energy homeostasis, and mitigating inflammation.http://www.sciencedirect.com/science/article/pii/S2589004224025173Biochemical mechanism
spellingShingle Anindya Ghosh
Isabelle Chénier
Yat Hei Leung
Abel K. Oppong
Marie-Line Peyot
S. R. Murthy Madiraju
Irina Al-Khairi
Jehad Abubaker
Fahd Al-Mulla
Marc Prentki
Mohamed Abu-Farha
Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice
iScience
Biochemical mechanism
title Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice
title_full Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice
title_fullStr Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice
title_full_unstemmed Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice
title_short Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice
title_sort adipocyte angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice
topic Biochemical mechanism
url http://www.sciencedirect.com/science/article/pii/S2589004224025173
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