Adipocyte lipin 1 is positively associated with metabolic health in humans and regulates systemic metabolism in mice.
Adipocyte lipin 1 is positively associated with metabolic health in humans and regulates systemic metabolism in mice.
复制标题
脂肪细胞脂质 1 与人类的代谢健康呈正相关，并调节小鼠的全身代谢。
DOI：
10.1101/2023.02.01.526676
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Brestoff,Jonatha
中科院分区：
文献类型：
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作者：
LaPoint,Andrew;Singer,JasonM;Ferguson,Daniel;Shew,TrevorM;Renkemeyer,MKatie;Palacios,Hector;Field,Rachael;Shankaran,Mahalakshmi;Smith,GordonI;Yoshino,Jun;He,Mai;Patti,GaryJ;Hellerstein,MarcK;Klein,Samuel;Brestoff,Jonatha
脂肪组织功能障碍被认为是促进肝脏脂肪变性和全身性胰岛素抵抗的发展，但许多涉及的机制仍不清楚。Lipin 1催化磷脂酸转化为二酰基甘油（DAG），这是甘油三酯合成的倒数第二步，对脂质储存至关重要。在此我们发现，与瘦型受试者相比，肥胖者脂肪组织LPIN 1表达降低，低LPIN 1表达与多组织胰岛素抵抗和肝脏新生脂肪生成率增加相关。全面的代谢和多组学表型分析表明，脂肪细胞特异性Lpin 1-/-小鼠具有代谢不健康的表型，包括肝脏和骨骼肌胰岛素抵抗、肝脏脂肪变性、肝脏新生脂肪生成增加以及高脂饮食加重的非酒精性脂肪性肝炎的转录组学特征。我们的结论是，脂肪细胞lipin 1介导的脂质储存对于保护脂肪组织和全身代谢健康是至关重要的，其损失易使小鼠患非酒精性脂肪性肝炎。
Dysfunctional adipose tissue is believed to promote the development of hepatic steatosis and systemic insulin resistance, but many of the mechanisms involved are still unclear. Lipin 1 catalyzes the conversion of phosphatidic acid to diacylglycerol (DAG), the penultimate step of triglyceride synthesis, which is essential for lipid storage. Herein we found that adipose tissueLPIN1expression is decreased in people with obesity compared to lean subjects and lowLPIN1expression correlated with multi-tissue insulin resistance and increased rates of hepatic de novo lipogenesis. Comprehensive metabolic and multi-omic phenotyping demonstrated that adipocyte-specificLpin1-/-mice had a metabolically-unhealthy phenotype, including liver and skeletal muscle insulin resistance, hepatic steatosis, increased hepatic de novo lipogenesis, and transcriptomic signatures of nonalcoholic steatohepatitis that was exacerbated by high-fat diets. We conclude that adipocyte lipin 1-mediated lipid storage is vital for preserving adipose tissue and systemic metabolic health and its loss predisposes mice to nonalcoholic steatohepatitis.