Glucocorticoid aggravates bone micro-architecture deterioration and skeletal muscle atrophy in mice fed on high-fat diet

Abstract

High fat diet (HFD) induced obesity has deleterious effect on bone micro-architecture and is associated with low-grade chronic inflammation. Exogenous glucocorticoids (GC) are used to treat inflammatory conditions but with concomitant adverse effect on musculoskeletal system. This study aims to highlight the effect of exogenous GCs on musculoskeletal system in mice fed on HFD. Adult BALB/c mice were fed either normal chow or high fat diet and were exogenously administered with GC for 10 weeks. At the end of the study, animals were autopsied and bone, muscle, serum samples were collected for micro-CT, gene expression and histological study. HFD induced obesity resulted in deterioration in bone micro-architecture predominant in trabecular region of long bones and was significantly amplified with GC administration. Approximately, 37% and 25% loss in femoral and tibial bone volume was observed in obese animals with exogenous GC. Further, deteriorating bone pathology was apparent from reduced bone mineral density (BMD) and bone strength parameter which was correlated to alteration in osteoblast and adipocytes pool of cells in bone marrow. Transcriptional analysis of osteoblast marker genes, bone morphogenetic protein 2 (BMP-2), osteocalcin (OCN) exhibited decreased formation. Moreover, similar degeneration was observed in skeletal muscle physiology with stimulation in muscle atrophy genes atrogin-1, muscle ring finger motif-1 (MuRF-1) and inflammatory markers accompanied with intra-myocellular lipid accumulation. Thus, our results showed that detrimental effect of GC on bone and skeletal muscle is aggravated with HFD, attributed to alteration in bone marrow cell population and skeletal muscle atrophy.