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Enrichment of Short-Chain Ceramides and Free Fatty Acids in the Skin Epidermis, Liver, and Kidneys of db/db Mice, a Type 2 Diabetes Mellitus Model

  • Kim, Minjeong (Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University) ;
  • Jeong, Haengdueng (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Lee, Buhyun (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Cho, Yejin (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Yoon, Won Kee (Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Cho, Ahreum (Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University) ;
  • Kwon, Guideock (Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University) ;
  • Nam, Ki Taek (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Ha, Hunjoo (Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University) ;
  • Lim, Kyung-Min (Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University)
  • Received : 2018.11.04
  • Accepted : 2018.12.17
  • Published : 2019.09.01

Abstract

Patients with diabetes mellitus (DM) often suffer from diverse skin disorders, which might be attributable to skin barrier dysfunction. To explore the role of lipid alterations in the epidermis in DM skin disorders, we quantitated 49 lipids (34 ceramides, 14 free fatty acids (FFAs), and cholesterol) in the skin epidermis, liver, and kidneys of db/db mice, a Type 2 DM model, using UPLC-MS/MS. The expression of genes involved in lipid synthesis was also evaluated. With the full establishment of hyperglycemia at the age of 20 weeks, remarkable lipid enrichment was noted in the skin of the db/db mice, especially at the epidermis and subcutaneous fat bed. Prominent increases in the ceramides and FFAs (>3 fold) with short or medium chains ($LXR{\alpha}/{\beta}$ and $PPAR{\gamma}$, nuclear receptors promoting lipid synthesis, lipid synthesis enzymes such as elongases 1, 4, and 6, and fatty acid synthase and stearoyl-CoA desaturase were highly expressed in the skin and livers of the db/db mice. Collectively, our study demonstrates an extensive alteration in the skin and systemic lipid profiles of db/db mice, which could contribute to the development of skin disorders in DM.

Keywords

References

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