Low expression of IL-18 and IL-18 receptor in human skeletal muscle is associated with systemic and intramuscular lipid metabolism—Role of HIV lipodystrophy
| Autor: | Birgitte Lindegaard, Thine Hvid, Helene Wolsk Mygind, Ole Hartvig-Mortensen, Thomas Grøndal, Julie Abildgaard, Jan Gerstoft, Bente Klarlund Pedersen, Marcin Baranowski |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Receptors Interleukin-18 Muscle Skeletal/metabolism Multidisciplinary Lipodystrophy lcsh:R Interleukin-18 lcsh:Medicine Correction HIV Infections/complications HIV Infections Middle Aged Lipid Metabolism 03 medical and health sciences 030104 developmental biology Humans lcsh:Q Receptors Interleukin-18/metabolism Lipodystrophy/complications Interleukin-18/metabolism lcsh:Science Muscle Skeletal |
| Zdroj: | PLoS ONE Lindegaard, B, Hvid, T, Wolsk Mygind, H, Mortensen, O H, Grøndal, T, Abildgaard, J, Gerstoft, J, Pedersen, B K & Baranowski, M 2018, ' Low expression of IL-18 and IL-18 receptor in human skeletal muscle is associated with systemic and intramuscular lipid metabolism : Role of HIV lipodystrophy ', PLoS ONE, vol. 13, no. 1, e0186755 . https://doi.org/10.1371/journal.pone.0186755 PLoS ONE, Vol 13, Iss 1, p e0186755 (2018) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0186755 |
| Popis: | INTRODUCTION: Interleukin (IL)-18 is involved in regulation of lipid and glucose metabolism. Mice lacking whole-body IL-18 signalling are prone to develop weight gain and insulin resistance, a phenotype which is associated with impaired fat oxidation and ectopic skeletal muscle lipid deposition. IL-18 mRNA is expressed in human skeletal muscle but a role for IL-18 in muscle has not been identified. Patients with HIV-infection and lipodystrophy (LD) are characterized by lipid and glucose disturbances and increased levels of circulating IL-18. We hypothesized that skeletal muscle IL-18 and IL-18 receptor (R) expression would be altered in patients with HIV-lipodystrophy.DESIGN AND METHODS: Twenty-three HIV-infected patients with LD and 15 age-matched healthy controls were included in a cross-sectional study. Biopsies from the vastus lateralis muscle were obtained and IL-18 and IL-18R mRNA expression were measured by real-time PCR and sphingolipids (ceramides, sphingosine, sphingosine-1-Phosphate, sphinganine) were measured by HPLC. Insulin resistance was assessed by HOMA and the insulin response during an OGTT.RESULTS: Patients with HIV-LD had a 60% and 54% lower level of muscular IL-18 and IL-18R mRNA expression, respectively, compared to age-matched healthy controls. Patients with HIV-LD had a trend towards increased levels of ceramide (18.3±4.7 versus 14.8±3.0,p = 0.06) and sphingosine (0.41±0.13 versus 0.32±0.07, and lower level of sphinganine (p = 0.06). Low levels of muscle IL-18 mRNA correlated to high levels of ceramides (r = -0.31, p = 0.038) and sphingosine-1P (r = -0.29, p = 0.046) in skeletal muscle, whereas such a correlation was not found in healthy controls. Low expression of IL-18 mRNA in skeletal muscle correlated to elevated concentration of circulating triglycerides (Rp = -0.73, pCONCLUSION: IL-18 (mRNA) in skeletal muscle appears to be involved in the regulation of intramuscular lipid metabolism and hypertriglyceridemia. |
| Databáze: | OpenAIRE |
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