Abstract
Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor-dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Bile Acids and Salts / administration & dosage
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Bile Acids and Salts / blood
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Bile Acids and Salts / metabolism*
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Cell Count
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Cholesterol 7-alpha-Hydroxylase / genetics
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Cholestyramine Resin / administration & dosage
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Cholestyramine Resin / pharmacology
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Cholic Acid / administration & dosage
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Cytokines / genetics
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Cytokines / metabolism
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DNA Replication
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Diet
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Forkhead Box Protein M1
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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Gene Expression Regulation
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Genes, myc
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Growth Substances / genetics
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Growth Substances / metabolism
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Hepatectomy
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Hepatocytes / cytology
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Homeostasis
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Liver / cytology
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Liver / metabolism
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Liver / physiology*
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Liver Regeneration*
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Mice
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Mice, Knockout
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Proto-Oncogene Proteins c-myc / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Cytoplasmic and Nuclear / genetics
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Signal Transduction*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Bile Acids and Salts
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Cytokines
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DNA-Binding Proteins
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Forkhead Box Protein M1
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Forkhead Transcription Factors
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Foxm1 protein, mouse
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Growth Substances
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Myc protein, mouse
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Proto-Oncogene Proteins c-myc
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Transcription Factors
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nuclear receptor subfamily 0, group B, member 2
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farnesoid X-activated receptor
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Cholestyramine Resin
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Cholesterol 7-alpha-Hydroxylase
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Cyp7a1 protein, mouse
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Cholic Acid