| Brown Fat Lipoatrophy and Increased Visceral Adiposity through a Concerted Adipocytokines Overexpression Induces Vascular Insulin Resistance and Dysfunction. | |
| | |
MedLine Citation:
|
PMID: 22253415 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
In this study, we analyzed the role played by concerted expression of adipocytokines associated with brown fat lipoatrophy and increased visceral adiposity on triggering vascular insulin resistance and dysfunction in brown adipose tissue (BAT) insulin receptor knockout (BATIRKO) mice. In addition, we assessed whether vascular insulin resistance may aggravate vascular damage. The 52-wk-old, but not 33-wk-old, BATIRKO mice had a significant decrease of BAT mass associated with a significant increase of visceral white adipose tissue (WAT) mass, without changes in body weight. Brown fat lipoatrophy and increased visceral adiposity enhanced the concerted expression of adipocytokines (TNF-α, leptin, and plasminogen activator inhibitor 1) and nuclear factor-κB binding activity in BAT and visceral WAT, mainly in the gonadal depot, and aorta. Although those mice showed insulin sensitivity in the liver and skeletal muscle, insulin signaling in WAT (gonadal depot) and aorta was markedly impaired. Treatment with anti-TNF-α antibody impaired the inflammatory activity in visceral adipose tissue, attenuated insulin resistance in WAT and aorta and induced glucose tolerance. Finally, 52-wk-old BATIRKO mice showed vascular dysfunction, macrophage infiltration, oxidative stress, and a significant increase of gene markers of endothelial activation and inflammation, the latter effect being totally reverted by anti-TNF-α antibody treatment. Our results suggest that brown fat lipoatrophy and increased visceral adiposity through the concerted overexpression of cytoadipokines induces nuclear factor-κB-mediated inflammatory signaling, vascular insulin resistance, and vascular dysfunction. Inhibition of inflammatory activity by anti-TNF-α antibody treatment attenuates vascular insulin resistance and impairs gene expression of vascular dysfunction markers. |
| | |
Authors:
|
Almudena Gómez-Hernández; Yolanda F Otero; Natalia de Las Heras; Oscar Escribano; Victoria Cachofeiro; Vicente Lahera; Manuel Benito |
Related Documents
:
|
20616745 - The right fiber for the right disease: an update on the psyllium seed husk and the meta... 22023455 - Blockade of kinin b(1) receptor reverses plasma fatty acids composition changes and bo... 15008835 - Aggregation of features of the metabolic syndrome is associated with increased prevalen... 21293115 - Beta-cell dysfunction and insulin resistance after subarachnoid haemorrhage. 18648765 - Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction o... 145645 - The early phase of insulin release in man--a new method for quantitative analysis. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-17 |
Journal Detail:
|
Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-18 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Biochemistry and Molecular Biology Department (A.G.-H., Y.F.O., O.E., M.B.), School of Pharmacy, and Physiology Department (N.d.l.H., V.C., V.L.), School of Medicine, Complutense University of Madrid; Biomedical research network (CIBER) of Diabetes and Related Metabolic Diseases (A.G.-H., Y.F.O., O.E., M.B.); and Spanish Network of Cardiovascular Research (N.d.l.H., V.C., V.L.), Madrid 28040, Spain. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Antiapolipoprotein A-1 IgG Chronotropic Effects Require Nongenomic Action of Aldosterone on L-Type C...
Next Document: Uncovering novel reproductive defects in neurokinin B receptor null mice: closing the gap between mi...