Impaired Ribosome Biogenesis and Skeletal Muscle Growth in a Murine Model of Inflammatory Bowel Disease. Issue 2 (February 2016)

• Record Type: Journal Article
• Authors: Figueiredo, Vandre C.; Markworth, James F.; Durainayagam, Brenan R.; Pileggi, Chantal A.; Roy, Nicole C.; Barnett, Matthew P. G.; Cameron-Smith, David
• Is Part Of: Inflammatory bowel diseases. Volume 22:Issue 2(2016:Feb.)
• Publication Date: 2016-02
• Subjects: ribosomal RNA -- immunoglobulin -- Crohn's disease -- sarcopenia; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000000616
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : 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 muscles. Methods: Il10 −/− and C57BL/6 wild-type (WT) mice were inoculated with intestinal bacteria to induce colon inflammation at the fifth week of age. Skeletal muscles were collected between 7 and 14 weeks of age for analysis of muscle weight, myofiber cross-sectional area (CSA), and molecular markers of inflammation and anabolism pathways, with a focus on ribosome biogenesis. Results: Il10 −/− animals that developed colon inflammation had a marked increase in muscle immunoglobulin G (IgG) compared with WT. Inflamed Il10 −/− animals had impaired muscle mass gain and smaller myofiber 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. Abstract : Article first published online 21 October 2015.Supplemental Digital Content is Available in the Text.