Screening for Adiponectin Secretion Regulators

• Published in: Vitamins and Hormones Vol. 90; pp. 125 - 141
• Main Authors: Hino, Kyosuke, Nagata, Hidetaka
• Format: Book Chapter Journal Article
• Language: English
• Published: United States Elsevier Science & Technology 2012
• Subjects: 3T3-L1 Cells; Adipocytes - secretion; Adiponectin; Adiponectin - genetics; Adiponectin - secretion; Animals; CCAAT-Enhancer-Binding Protein-alpha - physiology; Cytokines - physiology; Forkhead Box Protein O1; Forkhead Transcription Factors - physiology; Gene Expression Regulation; High-throughput screening; Humans; Mice; Peroxisome proliferator-activated receptor-γ; PPAR gamma - physiology; Regulator; Transcription factor; Transcription Factors - physiology; Tumor necrosis factor α; High-throughput screening; Regulator; Transcription factor; Tumor necrosis factor α; Peroxisome proliferator-activated receptor-γ; Adiponectin
• ISBN: 9780123983138; 0123983134
• ISSN: 0083-6729; 2162-2620
• DOI: 10.1016/B978-0-12-398313-8.00005-1

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.