Abstract
Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires the enzymatic activity of lipases. We showed that genetic inactivation of adipose triglyceride lipase (ATGL) in mice increases adipose mass and leads to triacylglycerol deposition in multiple tissues. ATGL-deficient mice accumulated large amounts of lipid in the heart, causing cardiac dysfunction and premature death. Defective cold adaptation indicated that the enzyme provides FFAs to fuel thermogenesis. The reduced availability of ATGL-derived FFAs leads to increased glucose use, increased glucose tolerance, and increased insulin sensitivity. These results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipocytes / cytology
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Adipocytes / metabolism
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Adipose Tissue / anatomy & histology
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Adipose Tissue / enzymology*
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Adipose Tissue / metabolism
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Adipose Tissue, Brown / enzymology
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Animals
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Blood Glucose / metabolism
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Carboxylic Ester Hydrolases / deficiency
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Carboxylic Ester Hydrolases / genetics
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Carboxylic Ester Hydrolases / metabolism*
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Cell Size
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Energy Metabolism*
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Fatty Acids, Nonesterified / blood
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Fatty Acids, Nonesterified / metabolism
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Female
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Heart Failure / pathology
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Homeostasis
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Insulin / blood
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Isoproterenol / pharmacology
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Kidney / metabolism
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Lipase / deficiency
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Lipase / genetics
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Lipase / metabolism*
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Lipids / blood
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Lipolysis* / drug effects
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Male
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Mice
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Myocardium / metabolism
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Myocardium / pathology
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Myocytes, Cardiac / cytology
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Myocytes, Cardiac / metabolism
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Oxygen Consumption
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Testis / metabolism
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Thermogenesis
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Triglycerides / metabolism*
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Ventricular Dysfunction, Left / physiopathology
Substances
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Blood Glucose
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Fatty Acids, Nonesterified
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Insulin
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Lipids
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Triglycerides
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Carboxylic Ester Hydrolases
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Lipase
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PNPLA2 protein, mouse
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Isoproterenol