Linked Life Data

20858755

Source:http://linkedlifedata.com/resource/pubmed/id/20858755

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-11-30
pubmed:abstractText
The hypothalamic-pituitary-thyroid (HPT) axis is a major contributor in maintaining energy expenditure and body weight, and the adipocyte hormone leptin regulates this axis by increasing TRH levels in the fed state. Leptin stimulates TRH directly in the hypothalamic paraventricular nucleus (PVN; direct pathway) and indirectly by regulating proopiomelnocortin neurons in the hypothalamic arcuate nucleus (ARC; indirect pathway). Whereas the indirect pathway is fully functional in lean animals, it is inactive during diet-induced obesity (DIO) because of the establishment of leptin resistance. Despite this, the HPT axis activity in obese humans and rodents remains within the normal levels or slightly higher. Therefore, in this study, we aimed to determine the mechanism(s) by which the HPT axis is still active despite leptin resistance. With a combination of using the Sprague-Dawley rat physiological model and the Zuker rat that bears a mutation in the leptin receptor, we were able to demonstrate that under DIO conditions the HPT axis is regulated at the central level, but only through the direct pathway of leptin action on TRH neurons. Deiodinase enzymes, which are present in many tissues and responsible for converting thyroid hormones, were not statistically different between lean and DIO animals. These data suggest that the increase in T(4/3) seen in obese animals is due mostly to central leptin action. We also found that T(3) feedback inhibition on the prepro-TRH gene is controlled partially by leptin-induced pSTAT3 signaling via the TRH promoter. This interactive relationship between T(3) and pSTAT3 signaling appears essential to maintain the HPT axis at normal levels in conditions such as obesity.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1522-1555
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
299
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E976-89
pubmed:dateRevised
2011-2-23
pubmed:meshHeading
pubmed-meshheading:20858755-Analysis of Variance, pubmed-meshheading:20858755-Animals, pubmed-meshheading:20858755-Blotting, Western, pubmed-meshheading:20858755-Body Temperature, pubmed-meshheading:20858755-Diet, pubmed-meshheading:20858755-Energy Metabolism, pubmed-meshheading:20858755-Hypothalamo-Hypophyseal System, pubmed-meshheading:20858755-Hypothalamus, pubmed-meshheading:20858755-Immunohistochemistry, pubmed-meshheading:20858755-Leptin, pubmed-meshheading:20858755-Linear Models, pubmed-meshheading:20858755-Male, pubmed-meshheading:20858755-Neurons, pubmed-meshheading:20858755-Obesity, pubmed-meshheading:20858755-Radioimmunoassay, pubmed-meshheading:20858755-Rats, pubmed-meshheading:20858755-Rats, Sprague-Dawley, pubmed-meshheading:20858755-Rats, Zucker, pubmed-meshheading:20858755-Receptors, Leptin, pubmed-meshheading:20858755-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20858755-Signal Transduction, pubmed-meshheading:20858755-Thyroid Gland, pubmed-meshheading:20858755-Thyrotropin-Releasing Hormone, pubmed-meshheading:20858755-Thyroxine, pubmed-meshheading:20858755-Triiodothyronine
pubmed:year
2010
pubmed:articleTitle
Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level.
pubmed:affiliation
Div. of Endocrinology, Brown Medical School, Providence, RI 02903, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural