title: Screening for adiponectin secretion regulators.
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.
authors.affiliation: Genomic Science Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Konohana-Ku, Osaka, Japan. kyosuke-hino@ds-pharma.co.jp
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Hino
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Nagata
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D052242:Adiponectin; D022763:CCAAT-Enhancer-Binding Protein-alpha; D016207:Cytokines; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D047495:PPAR gamma; D014157:Transcription Factors