Skin fragility in obese diabetic mice: Possible involvement of elevated oxidative stress and upregulation of matrix metalloproteinases

Ai Ibuki, Tomoko Akase, Takashi Nagase, Takeo Minematsu, Gojiro Nakagami, Motoko Horii, Hiroshi Sagara, Takashi Komeda, Masayuki Kobayashi, Tsutomu Shimada, Masaki Aburada, Kotaro Yoshimura, Junko Sugama, Hiromi Sanada

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


The purpose of this study was to test the hypothesis that obese diabetic mice exhibit marked skin fragility, which is caused by increased oxidative stress and increased matrix metalloproteinase (MMP) gene expression in the subcutaneous adipose tissue. Scanning electron microscopy of skin samples from Tsumura-Suzuki obese diabetic (TSOD) mice revealed thinner collagen bundles, and decreased density and convolution of the collagen fibres. Furthermore, skin tensile strength measurements confirmed that the dorsal skin of TSOD mice was more fragile to tensile force than that of non-obese mice. The mRNA expressions of heme oxygenase 1 (Hmox1), a marker of oxidative stress, Mmp2 and Mmp14 were increased in the adipose tissue of TSOD mice. Antioxidant experiments were subsequently performed to determine whether the changes in collagen fibres and skin fragility were caused by oxidative stress. Strikingly, oral administration of the antioxidant dl-α-tocopherol acetate (vitamin E) decreased Hmox1, Mmp2 and Mmp14 mRNA expressions, and improved the skin tensile strength and structure of collagen fibres in TSOD mice. These findings suggest that the skin fragility in TSOD mice is associated with dermal collagen damage and weakened tensile strength, and that oxidative stress and MMP overexpression in the subcutaneous adipose tissue may, at least in part, affect dermal fragility via a paracrine pathway. These observations may contribute to novel clinical interventions, such as dietary supplementation with antioxidants or application of skin cream containing antioxidants, which may overcome skin fragility in obese patients with diabetes.

Original languageEnglish
Pages (from-to)178-183
Number of pages6
JournalExperimental Dermatology
Issue number3
Publication statusPublished - 2012 Mar


  • Collagen
  • Matrix metalloproteinases
  • Oxidative stress
  • Skin tensile strength
  • Subcutaneous adipose tissue

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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