Abstract
Autophagy recently has been shown to be involved in normal hepatic function and in pathological conditions such as non-alcoholic fatty liver disease. Adrenergic signalling also is an important regulator of hepatic metabolism and function. However, currently little is known about the potential role of adrenergic signaling on hepatic autophagy, and whether the β-adrenergic receptor itself may be a key regulator of autophagy. To address these issues, we investigated the actions of the β2-adrenergic receptor agonist, clenbuterol on hepatic autophagy. Surprisingly, we found that clenbuterol stimulated autophagy and autophagic flux in hepatoma cells, primary hepatocytes and in vivo. Similar effects also were observed with epinephrine treatment. Interestingly, propranolol caused a late block in autophagy in the absence and presence of clenbuterol, both in cell culture and in vivo. Thus, our results demonstrate that the β2-adrenergic receptor is a key regulator of hepatic autophagy, and that the β-blocker propranolol can independently induce a late block in autophagy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic beta-Agonists / administration & dosage
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Adrenergic beta-Antagonists / administration & dosage
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Animals
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Autophagy / genetics*
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Clenbuterol / administration & dosage
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Epinephrine / administration & dosage
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Hep G2 Cells
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Hepatocytes / drug effects
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Hepatocytes / metabolism*
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Humans
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Liver / drug effects
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Liver / metabolism*
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Mice
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Propranolol / administration & dosage
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Receptors, Adrenergic, beta-2 / metabolism*
Substances
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Adrenergic beta-Agonists
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Adrenergic beta-Antagonists
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Receptors, Adrenergic, beta-2
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Propranolol
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Clenbuterol
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Epinephrine
Grants and funding
This study was carried out with funds supplied by Singapore National Medical Research Council Grant [NMRC/CIRG/1340/2012] provided to Dr. Paul M. Yen, as well as by Duke-NUS Graduate Medical School Faculty Funds also to Dr. Paul M. Yen, sponsored by the Singapore Ministries of Health, Education, and Trade, as well as A*STAR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.