Linked Life Data

16400329

Source:http://linkedlifedata.com/resource/pubmed/id/16400329

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7075
pubmed:dateCreated
2006-1-26
pubmed:abstractText
While bile acids (BAs) have long been known to be essential in dietary lipid absorption and cholesterol catabolism, in recent years an important role for BAs as signalling molecules has emerged. BAs activate mitogen-activated protein kinase pathways, are ligands for the G-protein-coupled receptor (GPCR) TGR5 and activate nuclear hormone receptors such as farnesoid X receptor alpha (FXR-alpha; NR1H4). FXR-alpha regulates the enterohepatic recycling and biosynthesis of BAs by controlling the expression of genes such as the short heterodimer partner (SHP; NR0B2) that inhibits the activity of other nuclear receptors. The FXR-alpha-mediated SHP induction also underlies the downregulation of the hepatic fatty acid and triglyceride biosynthesis and very-low-density lipoprotein production mediated by sterol-regulatory-element-binding protein 1c. This indicates that BAs might be able to function beyond the control of BA homeostasis as general metabolic integrators. Here we show that the administration of BAs to mice increases energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin. This novel metabolic effect of BAs is critically dependent on induction of the cyclic-AMP-dependent thyroid hormone activating enzyme type 2 iodothyronine deiodinase (D2) because it is lost in D2-/- mice. Treatment of brown adipocytes and human skeletal myocytes with BA increases D2 activity and oxygen consumption. These effects are independent of FXR-alpha, and instead are mediated by increased cAMP production that stems from the binding of BAs with the G-protein-coupled receptor TGR5. In both rodents and humans, the most thermogenically important tissues are specifically targeted by this mechanism because they coexpress D2 and TGR5. The BA-TGR5-cAMP-D2 signalling pathway is therefore a crucial mechanism for fine-tuning energy homeostasis that can be targeted to improve metabolic control.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
439
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
484-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16400329-Adipose Tissue, Brown, pubmed-meshheading:16400329-Adiposity, pubmed-meshheading:16400329-Animals, pubmed-meshheading:16400329-Bile Acids and Salts, pubmed-meshheading:16400329-Body Weight, pubmed-meshheading:16400329-Carbon Dioxide, pubmed-meshheading:16400329-Cholic Acid, pubmed-meshheading:16400329-Cyclic AMP, pubmed-meshheading:16400329-Dietary Fats, pubmed-meshheading:16400329-Energy Metabolism, pubmed-meshheading:16400329-Gene Deletion, pubmed-meshheading:16400329-Homeostasis, pubmed-meshheading:16400329-Humans, pubmed-meshheading:16400329-Iodide Peroxidase, pubmed-meshheading:16400329-Liver, pubmed-meshheading:16400329-Mice, pubmed-meshheading:16400329-Mice, Inbred C57BL, pubmed-meshheading:16400329-Muscle, Skeletal, pubmed-meshheading:16400329-Muscle Cells, pubmed-meshheading:16400329-Oxygen Consumption, pubmed-meshheading:16400329-Receptors, G-Protein-Coupled, pubmed-meshheading:16400329-Thyroid Hormones
pubmed:year
2006
pubmed:articleTitle
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation.
pubmed:affiliation
Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural