Lamin A/C deficiency is associated with fat infiltration of muscle and bone

Jessica Tong, Wei Li, Christopher Vidal, Li Sze Yeo, Diane Fatkin, Gustavo Duque

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

Sarcopenia and osteopenia are two common components of the frailty syndrome that may share a common underlying mechanism. Since frailty has been associated with increased fat infiltration in muscle and bone, we hypothesized that lamin A/C, a protein of the nuclear envelope that regulates adipose differentiation, could be associated with the pathophysiology of both osteo and sarcopenia in the frailty syndrome. Four-week-old lamin A/C null (Lmna(-/-)), heterozygous (Lmna(+/-)) and wild type (WT) mice were sacrificed and their mid-thigh analyzed for fat infiltration using invasive (histology) and non-invasive (μCT) methods. Lmna(-/-) mice showed a significant increase in inter- (~4-fold) and intra-myofiber (~2.5-fold) fat and marrow fat infiltration (~40-fold), with a significant decrease in muscle volume (-42.8%) and bone volume (-21.8%), as compared with WT controls. Furthermore, fat infiltration happened concomitantly with a significant decline in muscle and bone strength in Lmna(-/-) mice. From a mechanistic approach, high levels of pro-adipogenic factors PPARγ and C/EBPα were associated with a reduction in myogenic and osteogenic factors from the Wnt-10b/β-catenin signalling pathway in Lmna(-/-) mice. In conclusion, lamin A/C could constitute the determinant factor in the pathogenesis and potential treatment of both sarcopenia and osteopenia, which are commonly observed in the frailty syndrome.

Original languageEnglish
Pages (from-to)552-559
Number of pages8
JournalMechanisms of Ageing and Development
Volume132
Issue number11-12
DOIs
Publication statusPublished - 11 Oct 2011
Externally publishedYes

Keywords

  • Adipocytes
  • Adipogenesis
  • Aged
  • Aging
  • Animals
  • Bone Diseases, Metabolic
  • Bone and Bones
  • Disease Models, Animal
  • Frail Elderly
  • Humans
  • Lamin Type A
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Development
  • Muscle, Skeletal
  • Osteogenesis
  • PPAR gamma
  • Sarcopenia
  • Signal Transduction
  • Journal Article
  • Research Support, Non-U.S. Gov't

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