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, the penultimate step of triglyceride synthesis, which is essential for lipid storage. Herein we found that adipose tissue LPIN1 expression is decreased in people with obesity compared with lean subjects, and low LPIN1 expression correlated with multi-tissue insulin resistance and increased rates of hepatic de novo lipogenesis. Comprehensive metabolic and multiomic phenotyping demonstrated that adipocyte-specific Lpin1^–/– mice had a metabolically unhealthy phenotype, including liver and skeletal muscle insulin resistance, hepatic steatosis, increased hepatic de novo lipogenesis, and transcriptomic signatures of metabolically associated 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 metabolically associated steatohepatitis.

中文翻译：

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脂肪细胞脂质蛋白 1 表达与人类代谢健康相关，并调节小鼠的全身代谢


功能失调的脂肪组织被认为会促进肝脂肪变性和全身胰岛素抵抗的发展，但所涉及的许多机制仍不清楚。Lipin 1 催化磷脂酸转化为甘油二酯，这是甘油三酯合成的倒数第二步，这对于脂质储存至关重要。在此，我们发现与瘦受试者相比，肥胖患者的脂肪组织 LPIN1 表达降低，低 LPIN1 表达与多组织胰岛素抵抗和肝脏新发脂肪生成速率增加相关。综合代谢和多组学表型表明，脂肪细胞特异性 Lpin1^–/– 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、肝脂肪变性、肝脏新发脂肪生成增加以及代谢相关脂肪性肝炎的转录组特征，高脂肪饮食加剧了这种情况。我们得出结论，脂肪细胞脂质蛋白 1 介导的脂质储存对于保护脂肪组织和全身代谢健康至关重要，其丢失使小鼠易患代谢相关的脂肪性肝炎。