Ageing prolongs inflammatory marker expression in regenerating rat skeletal muscles after injury

<p>Abstract</p> <p>Background</p> <p>Some of the most serious consequences of normal ageing relate to its effects on skeletal muscle, particularly significant wasting and associated weakness, termed "sarcopenia". The underlying mechanisms of sarcopenia have yet to be elucidated completely but an altered muscle inflammatory response after injury is a likely contributing factor. In this study we investigated age-related changes in the expression of numerous inflammatory markers linked to successful muscle regeneration.</p> <p>Methods</p> <p>Right extensor digitorum longus (EDL) muscles from young (3 month), adult (12 month) and old (24 month) male F344 rats were injected with bupivacaine hydrochloride to cause complete muscle fibre degeneration, then excised 12, 24, 36, and 72 hours later (n = 5/age group/time point). We used qRT-PCR to quantify the mRNA expression levels of the inflammatory markers TNFα, IFNγ, IL1, IL18, IL6, and CD18 as well as regenerative markers MyoD and myogenin.</p> <p>Results</p> <p>Inflammatory markers were all increased significantly in all age groups after myotoxic injury. There was a trend for expression of inflammatory markers to be higher in uninjured muscles of old rats, especially at 72 hours post injury where the expression levels of several markers was significantly higher in old compared with young and adult rats. There was also a decrease in the expression of regenerative markers in old rats at 72 hours post injury.</p> <p>Conclusion</p> <p>Our findings identify a prolonged inflammatory signature in injured muscles from old compared with young and adult rats together with a blunted expression of key markers of regeneration in muscles of old rats. Importantly, our findings identify potential targets for future therapeutic strategies for improving the regenerative capacity of skeletal muscle during ageing.</p

Statin Therapy Alters Lipid Storage in Diabetic Skeletal Muscle

While statins significantly reduce cholesterol levels and thereby reduce the risk of cardiovascular disease, the development of myopathy with statin use is a significant clinical side-effect. Recent guidelines recommend increasing inclusion criteria for statin treatment in diabetic individuals; however, the impact of statins on skeletal muscle health in those with diabetes (who already suffer from impairments in muscle health) is ill-defined. Here we investigate the effects of Fluvastatin treatment on muscle health in wild-type and streptozotocin (STZ)-induced diabetic mice. Wild-type and STZ-diabetic mice received diet enriched with 600 mg/kg Fluvastatin or control chow for 24 days. Muscle morphology, intra and extracellular lipid levels, and lipid transporter content was investigated. Our findings indicate that short-term Fluvastatin administration induced a myopathy that was not exacerbated by the presence of STZ-induced diabetes. Fluvastatin significantly increased ectopic lipid deposition within the muscle of STZ-diabetic animals, findings that were not seen with diabetes or statin treatment alone. Consistent with this observation, only Fluvastatin-treated diabetic mice downregulated protein expression of lipid transporters FAT/CD36 and FABPpm in their skeletal muscle. No differences in FAT/CD36 or FABPpm mRNA content were observed. Altered lipid compartmentalization resultant of a downregulation in lipid transporter content in STZ-induced diabetic skeletal muscle was apparent in the current investigation. Given the association between ectopic lipid deposition in skeletal muscle and the development of insulin-resistance, our findings highlight the necessity for more thorough investigations into the impact of statins in humans with diabetes

Intestinal Microbiota Contributes to Energy Balance, Metabolic Inflammation, and Insulin Resistance in Obesity

Obesity is associated with increased risk of developing metabolic diseases such as type 2 diabetes. The origins of obesity are multi-factorial, but ultimately rooted in increased host energy accumulation or retention. The gut microbiota has been implicated in control of host energy balance and nutrient extraction from dietary sources. The microbiota also impacts host immune status and dysbiosis-related inflammation can augment insulin resistance, independently of obesity. Advances in microbial metagenomic analyses and directly manipulating bacterial-host models of obesity have contributed to our understanding of the relationship between gut bacteria and metabolic disease. Foodborne, or drug-mediated perturbations to the gut microbiota can increase metabolic inflammation, insulin resistance, and dysglycemia. There is now some evidence that specific bacterial species can influence obesity and related metabolic defects such as insulin sensitivity. Components of bacteria are sufficient to impact obesity-related changes in metabolism. In fact, different microbial components derived from the bacterial cell wall can increase or decrease insulin resistance. Improving our understanding of the how components of the microbiota alter host metabolism is positioned to aid in the development of dietary interventions, avoiding triggers of dysbiosis, and generating novel therapeutic strategies to combat increasing rates of obesity and diabetes