Macrophage SREBP1 regulates skeletal muscle regeneration

Macrophages are essential for the proper inflammatory and reparative processes that lead to regeneration of skeletal muscle after injury. Recent studies have demonstrated close links between the function of activated macrophages and their cellular metabolism. Sterol regulatory element-binding protein 1 (SREBP1) is a key regulator of lipid metabolism and has been shown to affect the activated states of macrophages. However, its role in tissue repair and regeneration is poorly understood. Here we show that systemic deletion of Srebf1, encoding SREBP1, or macrophage-specific deletion of Srebf1a, encoding SREBP1a, delays resolution of inflammation and impairs skeletal muscle regeneration after injury. Srebf1 deficiency impairs mitochondrial function in macrophages and suppresses the accumulation of macrophages at sites of muscle injury. Lipidomic analyses showed the reduction of major phospholipid species in Srebf1-/- muscle myeloid cells. Moreover, diet supplementation with eicosapentaenoic acid restored the accumulation of macrophages and their mitochondrial gene expression and improved muscle regeneration. Collectively, our results demonstrate that SREBP1 in macrophages is essential for repair and regeneration of skeletal muscle after injury and suggest that SREBP1-mediated fatty acid metabolism and phospholipid remodeling are critical for proper macrophage function in tissue repair

Amplitude and area ratios of summating potential/action potential (SP/AP) in Meniere\u27s disease.

CONCLUSIONS: Our results suggest that summating potential/action potential (SP/AP) area ratio may not necessarily have higher sensitivity in the diagnosis of endolymphatic hydrops of Meniere\u27s disease (MD) than SP/AP amplitude ratio in transtympanic electrocochleography (ECochG). OBJECTIVE: Recent studies suggested that SP/AP area curve ratio was more sensitive to endolymphatic hydrops in comparison with SP/AP amplitude ratio in extratympanic ECochG. The purpose of the present study was to evaluate the utility of the SP/AP area curve ratio in transtympanic ECochG for the diagnosis of MD. PATIENTS AND METHODS: A retrospective chart review of 198 patients (209 ears) was conducted in cases of MD. RESULTS: With regard to SP/AP amplitude ratio, 57.1% in definite cases of MD (group 1), 39.6% in probable cases of MD (group 2), and 50.0% in the cases who had transformed from probable MD to definite MD (group 3) showed abnormally high values, respectively. Abnormally high values were observed in 43.9%, 27.7%, and 30.0% in SP/AP area ratio in groups 1, 2, and 3, respectively, indicating that abnormal values were observed more frequently in the amplitude ratio than in the area ratio in all three groups

DataSheet_1_Macrophage SREBP1 regulates skeletal muscle regeneration.pdf

Macrophages are essential for the proper inflammatory and reparative processes that lead to regeneration of skeletal muscle after injury. Recent studies have demonstrated close links between the function of activated macrophages and their cellular metabolism. Sterol regulatory element-binding protein 1 (SREBP1) is a key regulator of lipid metabolism and has been shown to affect the activated states of macrophages. However, its role in tissue repair and regeneration is poorly understood. Here we show that systemic deletion of Srebf1, encoding SREBP1, or macrophage-specific deletion of Srebf1a, encoding SREBP1a, delays resolution of inflammation and impairs skeletal muscle regeneration after injury. Srebf1 deficiency impairs mitochondrial function in macrophages and suppresses the accumulation of macrophages at sites of muscle injury. Lipidomic analyses showed the reduction of major phospholipid species in Srebf1-/- muscle myeloid cells. Moreover, diet supplementation with eicosapentaenoic acid restored the accumulation of macrophages and their mitochondrial gene expression and improved muscle regeneration. Collectively, our results demonstrate that SREBP1 in macrophages is essential for repair and regeneration of skeletal muscle after injury and suggest that SREBP1-mediated fatty acid metabolism and phospholipid remodeling are critical for proper macrophage function in tissue repair.</p