Changes in skeletal muscle and tendon structure and function following genetic inactivation of myostatin in rats

Myostatin is a negative regulator of skeletal muscle and tendon mass. Myostatin deficiency has been well studied in mice, but limited data are available on how myostatin regulates the structure and function of muscles and tendons of larger animals. We hypothesized that, in comparison to wild‐type (MSTN+/+) rats, rats in which zinc finger nucleases were used to genetically inactivate myostatin (MSTNΔ/Δ) would exhibit an increase in muscle mass and total force production, a reduction in specific force, an accumulation of type II fibres and a decrease and stiffening of connective tissue. Overall, the muscle and tendon phenotype of myostatin‐deficient rats was markedly different from that of myostatin‐deficient mice, which have impaired contractility and pathological changes to fibres and their extracellular matrix. Extensor digitorum longus and soleus muscles of MSTNΔ/Δ rats demonstrated 20–33% increases in mass, 35–45% increases in fibre number, 20–57% increases in isometric force and no differences in specific force. The insulin‐like growth factor‐1 pathway was activated to a greater extent in MSTNΔ/Δ muscles, but no substantial differences in atrophy‐related genes were observed. Tendons of MSTNΔ/Δ rats had a 20% reduction in peak strain, with no differences in mass, peak stress or stiffness. The general morphology and gene expression patterns were similar between tendons of both genotypes. This large rodent model of myostatin deficiency did not have the negative consequences to muscle fibres and extracellular matrix observed in mouse models, and suggests that the greatest impact of myostatin in the regulation of muscle mass may not be to induce atrophy directly, but rather to block hypertrophy signalling.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111244/1/tjp6572.pd

Leukocyte telomere length is inversely associated with a metabolic risk score in Mesoamerican children

ObjectiveLeukocyte telomere length (LTL) may be involved in the etiology of the metabolic syndrome (MetS). We examined the associations of LTL with MetS and its components among Mesoamerican children and their adult parents, in a region where MetS prevalence is high.MethodsWe conducted a cross- sectional study of 151 children aged 7- 12- years and 346 parents from the capitals of Belize, Honduras, Nicaragua, Costa Rica, Panama, and Chiapas State, Mexico. We quantified LTL by qPCR on DNA extracted from whole blood. In children, we created an age- and sex- standardized metabolic risk score using waist circumference (WC), the homeostasis model of insulin resistance (HOMA- IR), blood pressure, serum high- density lipoprotein (HDL) cholesterol, and serum triglycerides. In adults, MetS was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III definition. We estimated mean differences in metabolic risk score and prevalence ratios of MetS across quartiles of LTL using multivariable- adjusted linear and Poisson regression models, respectively.ResultsIn children, every 1 LTL z- score was related to an adjusted 0.05- units lower (95% CI: - 0.09, - 0.02, P =- 0.005) MetS risk score, through WC, HOMA- IR, and HDL. Among adults, LTL was not associated with MetS prevalence; however, every 1 LTL z- score was associated with an adjusted 34% lower prevalence of high fasting glucose (95% CI: 3%, 55%, p = .03).ConclusionsAmong Mesoamerican children, LTL is associated with an improved metabolic profile; among adults, LTL is inversely associated with the prevalence of high fasting glucose.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171621/1/ajhb23596_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171621/2/ajhb23596.pd