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Vitam Horm. 2012;90:125-41. doi: 10.1016/B978-0-12-398313-8.00005-1.

Screening for adiponectin secretion regulators.

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  • 1Genomic Science Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Konohana-Ku, Osaka, Japan. kyosuke-hino@ds-pharma.co.jp

Abstract

Adiponectin is an adipokine secreted from adipocytes and plays important roles in the suppression of metabolic syndromes that can result in type 2 diabetes, obesity, and atherosclerosis. Adiponectin is a promising drug target because a number of studies have shown that upregulation of adiponectin has a number of therapeutic benefits. Extensive efforts have revealed various adiponectin regulators, such as cytokines, transcription factors, and drugs. Cytokines, such as tumor necrosis factor α, IL-6, and IL-18, downregulate adiponectin production. On the other hand, transcription factors such as peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT-enhancer-binding protein α, and forkhead box O1 (FoxO1) upregulate adiponectin expression, although the activating transcription factor 3 and cAMP response element-binding protein downregulate it. Although a number of therapeutic drugs have been reported as adiponectin secretion regulators, most of them act through PPARγ-dependent mechanisms, leaving PPARγ-derived side effects as a concern. Using high-throughput screening, we have identified PPARγ-independent adiponectin secretion regulators as potential drug candidates with a novel mechanism of action.

[PubMed - indexed for MEDLINE]
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