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首页> 外文期刊>Endocrinology >Osteocalcin Protects Against Nonalcoholic Steatohepatitis in a Mouse Model of Metabolic Syndrome
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Osteocalcin Protects Against Nonalcoholic Steatohepatitis in a Mouse Model of Metabolic Syndrome

机译：骨钙素可预防代谢综合征小鼠模型中的非酒精性脂肪性肝炎

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Nonalcoholic fatty liver disease, particularly its more aggressive form, nonalcoholic steatohepatitis (NASH), is associated with hepatic insulin resistance. Osteocalcin, a protein secreted by osteoblast cells in bone, has recently emerged as an important metabolic regulator with insulin-sensitizing properties. In humans, osteocalcin levels are inversely associated with liver disease. We thus hypothesized that osteocalcin may attenuate NASH and examined the effects of osteocalcin treatment in middle-aged (12-mo-old) male Ldlr(-/-) mice, which were fed a Western-style high-fat, high-cholesterol diet for 12 weeks to induce metabolic syndrome and NASH. Mice were treated with osteocalcin (4.5 ng/h) or vehicle for the diet duration. Osteocalcin treatment not only protected against Western-style high-fat, high-cholesterol diet-induced insulin resistance but substantially reduced multiple NASH components, including steatosis, ballooning degeneration, and fibrosis, with an overall reduction in nonalcoholic fatty liver disease activity scores. Further, osteocalcin robustly reduced expression of proinflammatory and profibrotic genes (Cd68, Mcp1, Spp1, and Col1a2) in liver and suppressed inflammatory gene expression in white adipose tissue. In conclusion, these results suggest osteocalcin inhibits NASH development by targeting inflammatory and fibrotic processes.
机译：非酒精性脂肪肝疾病，特别是其更具侵略性的形式，非酒精性脂肪性肝炎（NASH）与肝胰岛素抵抗有关。骨钙素是骨骼中成骨细胞分泌的一种蛋白质，最近已成为具有胰岛素敏感性的重要代谢调节剂。在人类中，骨钙蛋白水平与肝脏疾病成反比。因此，我们假设骨钙素可能会减弱NASH，并研究了骨钙素治疗对中老年（12个月大）雄性Ldlr（-/-）小鼠的影响，这些小鼠接受了西式高脂，高胆固醇饮食持续12周以诱发代谢综合征和NASH。在饮食期间，用骨钙蛋白（4.5 ng / h）或媒介物治疗小鼠。骨钙素治疗不仅可以抵御西方式的高脂肪，高胆固醇饮食诱导的胰岛素抵抗，而且可以显着减少多种NASH成分，包括脂肪变性，球囊变性和纤维化，从而总体上减少非酒精性脂肪肝疾病活动评分。此外，骨钙素强烈降低了肝脏中促炎和纤维化基因（Cd68，Mcp1，Spp1和Col1a2）的表达，并抑制了白色脂肪组织中的炎症基因表达。总之，这些结果表明骨钙素通过靶向炎症和纤维化过程来抑制NASH的发展。

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