Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action.
Adiponectin mediates anti-diabetic effects via increasing hepatic insulin sensitivity and direct metabolic effects. In the present study, we conducted a comprehensive and unbiased metabolomic profiling of liver tissue from AdKO (adiponectin-knockout) mice, with and without adiponectin supplementation, fed on an HFD (high-fat diet) to derive insight into the mechanisms and consequences of insulin resistance. Hepatic lipid accumulation and insulin resistance induced by the HFD were reduced by adiponectin. The HFD significantly altered levels of 147 metabolites, and bioinformatic analysis indicated that one of the most striking changes was the profile of increased lysophospholipids. These changes were largely corrected by adiponectin, at least in part via direct regulation of PLA2 (phospholipase A2) as palmitate-induced PLA2 activation was attenuated by adiponectin in primary hepatocytes. Notable decreases in several glycerolipids after the HFD were reversed by adiponectin, which also corrected elevations in several diacyglycerol and ceramide species. Our data also indicate that stimulation of ω-oxidation of fatty acids by the HFD is enhanced by adiponectin. In conclusion, this metabolomic profiling approach in AdKO mice identified important targets of adiponectin action, including PLA2, to regulate lysophospholipid metabolism and ω-oxidation of fatty acids.
Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3.
Ying
Y
Liu
Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3.
Sanjana
S
Sen
Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3 Department of Tropical Nutrition and Food Science, Mahidol University, Bangkok 10400, Thailand.
Sivaporn
S
Wannaiampikul
Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3.
Rengasamy
R
Palanivel
State Key Laboratory of Pharmaceutical Biotechnology, and Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong.
Ruby L C
RL
Hoo
The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, Canada, M5S 3E1.
Ruth
R
Isserlin
The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, Canada, M5S 3E1.
Gary D
GD
Bader
Department of Tropical Nutrition and Food Science, Mahidol University, Bangkok 10400, Thailand.
Rungsunn
R
Tungtrongchitr
Department of Medicine and Québec Heart & Lung Institute Research Centre, Université Laval, Québec City, Québec, Canada, G1V 4G5.
Yves
Y
Deshaies
State Key Laboratory of Pharmaceutical Biotechnology, and Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong.
Aimin
A
Xu
Department of Biology, York University, Toronto, Ontario, Canada, M3J 1P3 gsweeney@yorku.ca.
Gary
G
Sweeney
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008246:Lysophospholipids / Q000235:genetics / Q000378:metabolism*; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics; D051379:Mice; D018345:Mice, Knockout; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism
D052242:Adiponectin; C499919:Adipoq protein, mouse; D008246:Lysophospholipids; D054467:Phospholipases A2
adiponectin; high-fat diet; insulin; lipid; liver; phospholipase