Chemokine (C-X-C motif) ligand 1 is a myokine induced by palmitate and is required for myogenesis in mouse satellite cells.

AIM: The functional significance of the myokines, cytokines and peptides produced and released by muscle cells has not been fully elucidated. The purpose of this study was to identify a myokine with increased secretion levels in muscle cells due to saturated fatty acids and to examine the role of the identified myokine in the regulation of myogenesis. METHODS: Human primary myotubes and mouse C2C12 myotubes were used to identify the myokine; its secretion was stimulated by palmitate loading. The role of the identified myokine in the regulation of the activation, proliferation, differentiation and self-renewal was examined in mouse satellite cells (skeletal muscle stem cells). RESULTS: Palmitate loading promoted the secretion of chemokine (C-X-C motif) ligand 1 (CXCL1) in human primary myotubes, and it also increased CXCL1 gene expression level in C2C12 myotubes in a dose- and time-dependent manner. Palmitate loading increased the production of reactive oxygen species along with the activation of nuclear factor-kappa B (NF-κB) signalling. Pharmacological inhibition of NF-κB signalling attenuated the increase in CXCL1 gene expression induced by palmitate and hydrogen peroxide. Palmitate loading significantly increased CXC receptor 2 gene expression in undifferentiated cells. CXCL1 knockdown attenuated proliferation and myotube formation by satellite cells, with reduced self-renewal. CXCL1 knockdown also significantly decreased the Notch intracellular domain protein level. CONCLUSION: These results suggest that secretion of the myokine CXCL1 is stimulated by saturated fatty acids and that CXCL1 promotes myogenesis from satellite cells to maintain skeletal muscle homeostasis.

Serum amyloid A low-density lipoprotein levels and smoking status in obese Japanese patients.

Serum amyloid A low-density lipoprotein (SAA-LDL) is formed by an oxidative interaction and is considered to be a new marker related to oxidative modification of LDL. As the effect of smoking on oxidized LDL is of concern, this study investigated the association between SAA-LDL and smoking status. A total of 578 Japanese obese outpatients (mean ± SD age 50.5 ± 14.3 years) were studied. Smoking status was examined via a self-reported questionnaire. Cardio metabolic variables, including high-sensitivity Creactive protein (hsCRP), were analysed in addition to SAA-LDL. There was an increasing trend in SAA-LDL levels from non- to ex- to current smokers, and significantly higher SAA-LDL levels were observed in current smokers versus non-smokers (median SAA-LDL level 36 µg/ml versus 28 µg/ml, respectively). This significant difference was reduced after adjusting for multiple confounders, including lipid levels. Smoking may be associated with increased levels of SAA-LDL in an obese Japanese population, but further studies are needed.

Long-term inhalation of nitric oxide for a patient with primary pulmonary hypertension.

Primary pulmonary hypertension is a disease with a high mortality rate and for which there is no satisfactory medical treatment. The safety of long-term inhalation of nitric oxide (NO) as a treatment is described. A 9-year-old girl inhaled NO for 32 weeks, accompanied with oral administration of beraprost sodium. Although NO did not improve her long-term prognosis, it eased the patient's dyspnea and increased her blood oxygenation. At doses of 20 ppm or more, attempts to withdraw from inhaled NO seemed to lead to an immediate elevation of the pulmonary artery pressure. This rebound phenomenon did not happen at doses under 5 ppm. This case study suggests that long-term inhalation of NO is safe and effective, but that pulmonary hypertension may rebound following withdrawal at higher doses of NO.