Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice
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
Affiliations
Anindya Ghosh
Departments 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
Isabelle Chénier
Departments 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
Yat Hei Leung
Departments 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
Abel K. Oppong
Departments 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
Marie-Line Peyot
Departments 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
S. R. Murthy Madiraju
Departments 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
Irina Al-Khairi
Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait
Jehad Abubaker
Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait
Fahd Al-Mulla
Translational Research Department, Dasman Diabetes Institute, Dasman 15462, Kuwait
Marc Prentki
Departments 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 author
Mohamed Abu-Farha
Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; Translational Research Department, Dasman Diabetes Institute, Dasman 15462, Kuwait; Corresponding author
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.
