title: The effects of high-fat feeding on physical function and skeletal muscle extracellular matrix.
abstract: Skeletal muscle extracellular matrix (ECM) remodelling has been proposed as a feature of the pathogenic milieu associated with obesity and metabolic dysfunction. Whether muscle ECM is associated with impaired physical function in obese conditions is unknown. C57BL/6 mice were fed a high-fat diet (HFD) or chow for 5, 10 and 25 weeks. Non-invasive physiological tests (hang wire, hang mesh and grip strength) to assess neuromuscular function and motor co-ordination were performed. Genes related to ECM structure (COL1, COL3, COL6A2, SPARC), growth factors (TGFB1, TGFB2, CTGF, VEGF) and muscle function (DMD (Dp147), CPN3, DAG1) were measured in gastrocnemius muscle using real-time PCR and COL1, 3 and 6 protein were measured by western immunoblot. Compared with chow, HFD mice had two to six-fold lower muscle strength (hang wire test; raw data and multiplied by body weight) at all time-points (P<0.001) and two-fold lower hang mesh and grip strength at 10 weeks (P<0.05). At 5 weeks, COL1, COL3 and COL6 gene expression, but not protein levels were three to eight-fold lower in HFD compared with chow. In the HFD group at 5 weeks, greater COL3 and 6 gene expression were associated with poorer hang wire performance. For the first time, our results demonstrate links between muscle ECM structure and physical function in obesity.
authors.affiliation: The Charles Perkins Centre and School of Biological Sciences, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: C S
authors.initials: CS
authors.lastname: Tam
authors.affiliation: Sydney Medical School, and Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: J E
authors.initials: JE
authors.lastname: Power
authors.affiliation: Metabolism and Obesity Services Clinic, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: T P
authors.initials: TP
authors.lastname: Markovic
authors.affiliation: Sydney Medical School, and Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Yee
authors.affiliation: Motor Neuron Disease Research Group, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Morsch
authors.affiliation: Sydney Medical School, and Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.|Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: S V
authors.initials: SV
authors.lastname: McLennan
authors.affiliation: Sydney Medical School, and Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.|Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Twigg