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


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.

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