| Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level. | |
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MedLine Citation:
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PMID: 20858755 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Mario Perello; Isin Cakir; Nicole E Cyr; Amparo Romero; Ronald C Stuart; Franck Chiappini; Anthony N Hollenberg; Eduardo A Nillni |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-21 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 299 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-30 Completed Date: 2010-12-28 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E976-89 Citation Subset: IM |
Affiliation:
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Div. of Endocrinology, Brown Medical School, Providence, RI 02903, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Blotting, Western Body Temperature Diet Energy Metabolism Hypothalamo-Hypophyseal System / metabolism, physiopathology Hypothalamus / metabolism*, physiopathology Immunohistochemistry Leptin / metabolism* Linear Models Male Neurons / metabolism, physiology Obesity / etiology, metabolism*, physiopathology* Radioimmunoassay Rats Rats, Sprague-Dawley Rats, Zucker Receptors, Leptin Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Thyroid Gland / metabolism*, physiopathology* Thyrotropin-Releasing Hormone / metabolism Thyroxine / blood Triiodothyronine / blood |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK-078090/DK/NIDDK NIH HHS; R01-DK-58148/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Leptin; 0/Receptors, Leptin; 24305-27-9/Thyrotropin-Releasing Hormone; 6893-02-3/Triiodothyronine; 7488-70-2/Thyroxine |
| Comments/Corrections | |
Erratum In:
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Am J Physiol Endocrinol Metab. 2011 Feb;300(2):E422 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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