Impaired ribosome biogenesis and skeletal muscle growth in a murine model of inflammatory bowel disease

Background: Inflammation is a factor potentially underpinning skeletal muscle mass. Intestinal-derived inflammation in inflammatory bowel disease (IBD) results in loss of muscle mass; however the underlying mechanism is unclear. The interleukin 10 gene-deficient (Il10–/–) mouse is a genetically modified animal model of IBD that can be used to study the effect of intestinal-derived inflammation on muscle. Methods: Il10–/– and C57BL/6 wild type (WT) mice were inoculated with intestinal bacteria to induce colon inflammation at the 5th week of age. Skeletal muscles were collected between 7 to 14 weeks of age for analysis of muscle weight, myofiber cross-sectional area (CSA) and molecular markers of inflammation and anabolism pathways, with focus on ribosome biogenesis. Results: Il10–/– animals that developed colon inflammation had a marked increase in muscle immunoglobulin G (IgG) compared to WT. Inflamed Il10–/– animals had impaired muscle mass gain and smaller myofibre CSA. Intramuscular IgG deposition negatively correlated with muscle mass. After the onset of muscle inflammation, Il10–/– mice had decreased levels of total and ribosomal RNAs (45S, 28S, 18S and 5.8S rRNAs). Inflammation inversely correlated with muscle levels of total RNA and 28S rRNA, which in turn, positively correlated with muscle mass. The abundance of growth-related proteins (p70S6K and upstream binding factor, UBF) was decreased in Il10–/– mice. Conclusions: Muscle inflammation and associated decline of ribosome biogenesis lead to muscle growth impairment in Il10–/– mice. This may have implications for maintenance of muscle mass in conditions associated with chronic intestinal-derived inflammation.