title: Lamin A/C deficiency is associated with fat infiltration of muscle and bone.
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.
authors: Ageing Bone Research Program, Sydney Medical School Nepean, The University of Sydney, Penrith, NSW 2750, Australia.
authors: Jessica
authors: J
authors: Tong
authors: Wei
authors: W
authors: Li
authors: Christopher
authors: C
authors: Vidal
authors: Li Sze
authors: LS
authors: Yeo
authors: Diane
authors: D
authors: Fatkin
authors: Gustavo
authors: G
authors: Duque
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology*; D050156:Adipogenesis; D000368:Aged; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D016330:Frail Elderly; D006801:Humans; D034904:Lamin Type A / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D010012:Osteogenesis; D047495:PPAR gamma / Q000378:metabolism; D055948:Sarcopenia / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D034904:Lamin Type A; D047495:PPAR gamma; C440308:lamin C