title: Reduction and fragmentation of elastic fibers in the skin of obese mice is associated with altered mRNA expression levels of fibrillin-1 and neprilysin.
abstract: OBJECTIVE
  Our previous research suggested that obesity induces structural fragility in the skin. Elastic fibers impart strength and elasticity. In this study, we determined whether elastic fibers decrease in the skin of obese mice.
  
  
  METHODS
  To confirm alterations in elastic fiber content due to obesity, we used spontaneously obese model mice (TSOD) and control mice (TSNO). Furthermore, to evaluate the elastin structure and gene expression dependent on the severity of obesity, an obesity-enhanced mouse model was developed by feeding a high fat diet to TSOD (TSOD-HF). Back skin samples were stained with hematoxylin and eosin and Elastica van Gieson for microscopic examination, and the samples were stained for immunohistochemical analysis of neprilysin. Gene expression levels were determined using a real-time PCR system.
  
  
  RESULTS
  The abundance of elastic fibers beneath the epidermis was remarkably reduced and fragmented in TSOD as compared with TSNO. Fibrillin-1 mRNA levels in TSOD were significantly suppressed compared with those in TSNO, whereas neprilysin mRNA levels and immunohistochemical expression in TSOD were significantly increased, as compared with those in TSNO. The reduction of elastic fibers was enhanced and the expression levels of elastic fiber formed factors were significantly suppressed in TSOD-HF, as compared with those in the TSOD.
  
  
  CONCLUSIONS
  The abundance of elastic fibers was reduced and fragmented in obesity, suggesting that the reduction in elastic fibers is initially caused by increased neprilysin and decreased fibrillin-1 expression, which may inhibit formation and stabilization of elastic fibers, resulting in skin fragility in obesity.
authors.affiliation: a Department of Molecular Pharmacology and Neurobiology , Yokohama City University Graduate School of Medicine , Yokohama , Japan.|b Department of Biological Science and Nursing , Yokohama City University Graduate School of Medicine , Yokohama , Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Makihara
authors.affiliation: b Department of Biological Science and Nursing , Yokohama City University Graduate School of Medicine , Yokohama , Japan.
authors.forename: Moeko
authors.initials: M
authors.lastname: Hidaka
authors.affiliation: b Department of Biological Science and Nursing , Yokohama City University Graduate School of Medicine , Yokohama , Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: b Department of Biological Science and Nursing , Yokohama City University Graduate School of Medicine , Yokohama , Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Horie
authors.affiliation: c Department of Pathology , Yokohama City University Graduate School of Medicine , Yokohama , Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Mitsui
authors.affiliation: c Department of Pathology , Yokohama City University Graduate School of Medicine , Yokohama , Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: a Department of Molecular Pharmacology and Neurobiology , Yokohama City University Graduate School of Medicine , Yokohama , Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.affiliation: b Department of Biological Science and Nursing , Yokohama City University Graduate School of Medicine , Yokohama , Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Akase
mesh_terms: D000818:Animals; D004547:Elastic Tissue / Q000378:metabolism* / Q000473:pathology; D000071838:Fibrillin-1 / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008820:Mice, Obese; D015260:Neprilysin / Q000096:biosynthesis*; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D015260:Neprilysin; D012333:RNA, Messenger; C000605724:Fbn1 protein, mouse; D054392:Adipokines
keywords: Elastic fiber; fibrillin-1; neprilysin; obesity; skin