title: Overexpression of KLF15 transcription factor in adipocytes of mice results in down-regulation of SCD1 protein expression in adipocytes and consequent enhancement of glucose-induced insulin secretion.
abstract: Krüppel-like factor 15 (KLF15), a member of the Krüppel-like factor family of transcription factors, has been found to play diverse roles in adipocytes in vitro. However, little is known of the function of KLF15 in adipocytes in vivo. We have now found that the expression of KLF15 in adipose tissue is down-regulated in obese mice, and we therefore generated adipose tissue-specific KLF15 transgenic (aP2-KLF15 Tg) mice to investigate the possible contribution of KLF15 to various pathological conditions associated with obesity in vivo. The aP2-KLF15 Tg mice manifest insulin resistance and are resistant to the development of obesity induced by maintenance on a high fat diet. However, they also exhibit improved glucose tolerance as a result of enhanced insulin secretion. Furthermore, this enhancement of insulin secretion was shown to result from down-regulation of the expression of stearoyl-CoA desaturase 1 (SCD1) in white adipose tissue and a consequent reduced level of oxidative stress. This is supported by the findings that restoration of SCD1 expression in white adipose tissue of aP2-KLF15 Tg mice exhibited increased oxidative stress in white adipose tissue and reduced insulin secretion with hyperglycemia. Our data thus provide an example of cross-talk between white adipose tissue and pancreatic β cells mediated through modulation of oxidative stress.
authors.affiliation: Department of Molecular Metabolic Regulation, National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nagare
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakaue
authors.forename: Michihiro
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yongheng
authors.initials: Y
authors.lastname: Cao
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Inagaki
authors.forename: Mashito
authors.initials: M
authors.lastname: Sakai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takashima
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mori
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuki
authors.forename: Eijiro
authors.initials: E
authors.lastname: Watanabe
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamimura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohta
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002450:Cell Communication / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D051381:Rats; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D007328:Insulin; C467418:Klf15 protein, mouse; C520013:Klf15 protein, rat; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D005947:Glucose