| Restoration of adipose function in obese, glucose-tolerant men following pioglitazone treatment is associated with CCAAT enhancer-binding protein β upregulation. | |
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MedLine Citation:
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PMID: 22309242 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Obese adipose tissue (AT) exhibits increased macrophage number. Pro-inflammatory CD16+ peripheral monocyte numbers are also reported to increase with obesity. The current study was undertaken to simultaneously investigate obesity-associated changes in CD16+ monocytes and adipose tissue macrophages (ATM). In addition, a pilot randomised placebo controlled trial using the peroxisome proliferator-activated receptor (PPAR) agonists, pioglitazone and fenofibrate was performed to determine their effects on CD14+/CD16+ monocytes, ATM and cardiometabolic and adipose dysfunction indices. Obese glucose-tolerant men (n=32) were randomised to placebo, pioglitazone (30 mg/day) and fenofibrate (160 mg/day) for 12 weeks. A blood sample was taken to assess levels of serum inflammatory markers and circulating CD14+/CD16+ monocyte levels via flow cytometry. A subcutaneous (sc) AT biopsy was performed to determine adipocyte cell surface and AT macrophage (ATM) number, the latter was determined via assessment of CD68 expression by immunohistochemisty (IHC) and real time PCR. SC AT mRNA expression of CCAAT enhancer-binding protein β (CEBPβ), sterol regulatory element-binding protein 1c (SREBP1c), PPARγ2, insulin receptor substrate 1 (IRS-1), glucose transporter type 4 (GLUT 4) and tumour necrosis factor α (TNF-α) were also assessed. Comparisons were made between obese and lean controls (n=16) at baseline, and pre- and post-PPAR agonist treatment. Obese individuals had significantly increased adipocyte cell surface, % CD14+/CD16+ monocyte numbers and ATM number (all p=0.0001). Additionally, serum TNF-α levels were significantly elevated (p=0.017) and adiponectin levels reduced (total: p=0.0001; high: p=0.022) with obesity. ATM number and % of CD14+/CD16+ monocytes correlated significantly (P=0.05). Pioglitazone improved adiponectin levels significantly (p=0.0001), and resulted in the further significant enlargement of adipocytes (p=0.05), without effect on % CD14+/CD16+ or ATM number. Pioglitazone treatment also significantly increased sc AT expression of CEBPβ mRNA. The finding that improvements in obesity-associated insulin resistance following pioglitazone were associated with increased adipocyte cell surface and systemic adiponectin levels, supports the centrality of AT to the cardiometabolic derangement underlying the development of T2D and CVD. |
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Authors:
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Lesley Powell; Paul Crowe; Chenchi Kankara; Jennifer McPeake; David McCance; Ian S Young; Elisabeth R Trimble; Ann McGinty |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-6 |
Journal Detail:
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Title: Clinical science (London, England : 1979) Volume: - ISSN: 1470-8736 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7905731 Medline TA: Clin Sci (Lond) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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