Elucidation of pathophysiology of lipodystrophy and exploration of novel therapeutic targets of obesity and metabolic syndrome

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09779
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: National Cardiovascular Center Research Institute (2017-2019); Kyoto University (2016)
• Principal Investigator: Noguchi Michio 国立研究開発法人国立循環器病研究センター, オープンイノベーションセンター, 室長 (00432394)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 脂肪萎縮症 / 肥満症 / 脂肪蓄積

Outline of Final Research Achievements

In the present study, we addressed the molecular and cellular mechanisms of lipodystrophy using Seipin knockout rats (SKO rats). Histological analyses revealed the fibrosis of the tissue of SKO rats. Then, gene expression of fibrosis-related molecules such as extracellular matrix and matrix metalloproteinase, which were different types from those of adipose tissue fibrosis in obesity model animals, were elevated. Furthermore, we developed the methods of culture and adipogenic induction of stromal-vascular fraction of the adipose tissue of rats. After adipogenic induction, gene expression of mature adipocyte markers were remarkably decreased, while before the induction, gene expression of a set of fibrosis-related molecules were elevated.
These findings suggested the molecular mechanisms of fibrosis of residual adipose tissue in lipodystrophy.

Free Research Field

内分泌代謝

Academic Significance and Societal Importance of the Research Achievements

脂肪萎縮症は脂肪組織のexpandabilityの低下から脂肪組織における脂肪貯蔵の限界をきたし、肝臓や骨格筋等において異所性脂肪蓄積を引き起こす。脂肪組織量では対極にありながら脂肪萎縮症と肥満症は異所性脂肪蓄積や全身の糖脂質代謝異常を呈する点で非常に共通点が多い。脂肪組織の炎症・線維化に着目した本研究課題は脂肪萎縮症と肥満症の共通基盤病態の解明と肥満症・メタボリックシンドロームの新規治療標的の探索を行い、複数の治療標的候補分子を同定した。脂肪蓄積異常を呈する病態の統合的な理解と新たな創薬の研究領域の開発につながる。