title: Whole-transcriptome analysis of mouse adipose tissue in response to short-term caloric restriction.
abstract: Caloric restriction (CR) has been shown to extend the lifespan of many species by improving cellular function and organismal health. Additionally, fat reduction by CR may play an important role in lengthening lifespan and preventing severe age-related diseases. Interestingly, CR induced the greatest transcriptome change in the epididymal fat of mice in our study. In this transcriptome analysis, we identified and categorized 446 genes that correlated with CR level. We observed down-regulation of several signaling pathways, including insulin/insulin-like growth factor 1 (insulin/IGF-1), epidermal growth factor (EGF), transforming growth factor beta (TGF-β), and canonical wingless-type mouse mammary tumor virus integration site (Wnt). Many genes related to structural features, including extracellular matrix structure, cell adhesion, and the cytoskeleton, were down-regulated, with a strong correlation to the degree of CR. Furthermore, genes related to the cell cycle and adipogenesis were down-regulated. These biological processes are well-identified targets of insulin/IGF-1, EGF, TGF-β, and Wnt signaling. In contrast, genes involved in specific metabolic processes, including the tricarboxylic acid cycle and the electron transport chain were up-regulated. We performed in silico analysis of the promoter sequences of CR-responsive genes and identified two associated transcription factors, Paired-like homeodomain 2 (Pitx2) and Paired box gene 6 (Pax6). Our results suggest that strict regulation of signaling pathways is critical for creating the optimal energy homeostasis to extend lifespan.
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea.
authors.forename: Seung-Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea.
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Choi
authors.affiliation: Department of Food and Nutrition, Yonsei University, Seoul, 120-749, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Food and Nutrition, Yonsei University, Seoul, 120-749, Republic of Korea.
authors.forename: Taesun
authors.initials: T
authors.lastname: Park
authors.affiliation: Subtropical Animal Station, National Institute of Animal Science, Jeju, 690-150, Republic of Korea.
authors.forename: In-Cheol
authors.initials: IC
authors.lastname: Cho
authors.affiliation: Department of Statistics, Korea University, Seoul, 136-701, Republic of Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea. cklee2005@korea.ac.kr.
authors.forename: Cheol-Koo
authors.initials: CK
authors.lastname: Lee
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D004815:Epidermal Growth Factor / Q000096:biosynthesis; D005136:Eye Proteins / Q000096:biosynthesis; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D051379:Mice; D010084:Oxidation-Reduction; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D059467:Transcriptome / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D060449:Wnt Signaling Pathway; D000097577:Homeobox Protein PITX2
chemical_list: D004815:Epidermal Growth Factor; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000097577:Homeobox Protein PITX2; C000605732:Pax6 protein, mouse
keywords: Adipose tissue; Caloric restriction strength; Mice; Transcription factor; Transcriptome