Inhibiting Phosphatidylcholine Remodeling in Adipose Tissue Increases Insulin Sensitivity.

IF 6.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes Pub Date : 2023-11-01 DOI:10.2337/db23-0317

Mulin He, Zhiqiang Li, Victoria Sook Keng Tung, Meixia Pan, Xianlin Han, Oleg Evgrafov, Xian-Cheng Jiang

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Abstract

Cell membrane phosphatidylcholine (PC) composition is regulated by lysophosphatidylcholine acyltransferase (LPCAT); changes in membrane PC saturation are implicated in metabolic disorders. Here, we identified LPCAT3 as the major isoform of LPCAT in adipose tissue and created adipocyte-specific Lpcat3-knockout mice to study adipose tissue lipid metabolism. Transcriptome sequencing and plasma adipokine profiling were used to investigate how LPCAT3 regulates adipose tissue insulin signaling. LPCAT3 deficiency reduced polyunsaturated PCs in adipocyte plasma membranes, increasing insulin sensitivity. LPCAT3 deficiency influenced membrane lipid rafts, which activated insulin receptors and AKT in adipose tissue, and attenuated diet-induced insulin resistance. Conversely, higher LPCAT3 activity in adipose tissue from ob/ob, db/db, and high-fat diet-fed mice reduced insulin signaling. Adding polyunsaturated PCs to mature human or mouse adipocytes in vitro worsened insulin signaling. We suggest that targeting LPCAT3 in adipose tissue to manipulate membrane phospholipid saturation is a new strategy to treat insulin resistance.

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抑制脂肪组织中的磷脂酰胆碱重塑可增加胰岛素敏感性。

细胞膜磷脂酰胆碱（PC）的组成受溶血磷脂酰胆碱酰基转移酶（LPCAT）的调节；膜PC饱和度的变化与代谢紊乱有关。在这里，我们确定LPCAT3是脂肪组织中LPCAT的主要亚型，并创建了脂肪细胞特异性LPCAT3敲除小鼠来研究脂肪组织脂质代谢。转录组测序和血浆脂肪因子分析用于研究LPCAT3如何调节脂肪组织胰岛素信号传导。LPCAT3缺乏减少了脂肪细胞质膜中的多不饱和PC，增加了胰岛素敏感性。LPCAT3缺乏影响膜脂筏，膜脂筏激活脂肪组织中的胰岛素受体和AKT，并减弱饮食诱导的胰岛素抵抗。相反，ob/ob、db/db和高脂肪饮食喂养的小鼠脂肪组织中较高的LPCAT3活性降低了胰岛素信号传导。在体外将多不饱和PC添加到成熟的人类或小鼠脂肪细胞中会恶化胰岛素信号传导。我们认为，靶向脂肪组织中的LPCAT3来控制膜磷脂饱和度是治疗胰岛素抵抗的一种新策略。文章亮点：

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes 医学-内分泌学与代谢

CiteScore

12.50

自引率

2.60%

发文量

1968

审稿时长

1 months

期刊介绍： Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.