| A role for central nervous system PPAR-γ in the regulation of energy balance. | |
| | |
MedLine Citation:
|
PMID: 21532595 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that is activated by lipids to induce the expression of genes involved in lipid and glucose metabolism, thereby converting nutritional signals into metabolic consequences. PPAR-γ is the target of the thiazolidinedione (TZD) class of insulin-sensitizing drugs, which have been widely prescribed to treat type 2 diabetes mellitus. A common side effect of treatment with TZDs is weight gain. Here we report a previously unknown role for central nervous system (CNS) PPAR-γ in the regulation of energy balance. We found that both acute and chronic activation of CNS PPAR-γ, by either TZDs or hypothalamic overexpression of a fusion protein consisting of PPAR-γ and the viral transcriptional activator VP16 (VP16-PPAR-γ), led to positive energy balance in rats. Blocking the endogenous activation of CNS PPAR-γ with pharmacological antagonists or reducing its expression with shRNA led to negative energy balance, restored leptin sensitivity in high-fat-diet (HFD)-fed rats and blocked the hyperphagic response to oral TZD treatment. These findings have implications for the widespread clinical use of TZD drugs and for understanding the etiology of diet-induced obesity. |
| | |
Authors:
|
Karen K Ryan; Bailing Li; Bernadette E Grayson; Emily K Matter; Stephen C Woods; Randy J Seeley |
Related Documents
:
|
513025 - Fetal and placental weight relationships in the rat at days 13 and 17 of gestation. 12433665 - Developmental expression of enos in postnatal swine mesenteric artery. 1523265 - No persistent effect of preweaning nutrition on postweaning food intake, feeding effici... 9066725 - Stage of susceptibility to carcinogenicity of prenatal dietary fat exposure tested by b... 3315335 - Dietary suppression of prostaglandin synthesis does not accelerate doca/salt hypertensi... 3628545 - Influence of dietary fat on self-reported menstrual symptoms. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-05-01 |
Journal Detail:
|
Title: Nature medicine Volume: 17 ISSN: 1546-170X ISO Abbreviation: Nat. Med. Publication Date: 2011 May |
Date Detail:
|
Created Date: 2011-05-06 Completed Date: 2011-07-05 Revised Date: 2011-11-01 |
Medline Journal Info:
|
Nlm Unique ID: 9502015 Medline TA: Nat Med Country: United States |
Other Details:
|
Languages: eng Pagination: 623-6 Citation Subset: IM |
Affiliation:
|
Department of Internal Medicine, Division of Endocrinology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Blood-Brain Barrier Central Nervous System / drug effects, physiology* Energy Metabolism / physiology* Gene Expression Humans Hypoglycemic Agents / adverse effects, pharmacology Hypothalamus / drug effects, physiology Male PPAR gamma / agonists, antagonists & inhibitors, genetics, physiology* RNA, Small Interfering / genetics Rats Rats, Long-Evans Recombinant Fusion Proteins / genetics Thiazolidinediones / adverse effects, pharmacology Weight Gain / drug effects, physiology |
| Grant Support | |
ID/Acronym/Agency:
|
DK056863/DK/NIDDK NIH HHS; DK073505/DK/NIDDK NIH HHS; DK082173/DK/NIDDK NIH HHS; DK17844/DK/NIDDK NIH HHS; R01 DK017844-35/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Hypoglycemic Agents; 0/PPAR gamma; 0/RNA, Small Interfering; 0/Recombinant Fusion Proteins; 0/Thiazolidinediones; 122320-73-4/rosiglitazone |
| Comments/Corrections | |
Comment In:
|
Nat Med. 2011 May;17(5):544-5
[PMID:
21546969
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Structural adaptation of the plant protease Deg1 to repair photosystem II during light exposure.
Next Document: Brain PPAR-? promotes obesity and is required for the insulin-sensitizing effect of thiazolidinedion...