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LKB1 通过代谢和细胞因子相关信号通路,分别调节肌内和皮下脂肪细胞的脂肪生成。

LKB1 Differently Regulates Adipogenesis in Intramuscular and Subcutaneous Adipocytes through Metabolic and Cytokine-Related Signaling Pathways.

机构信息

College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.

Key Laboratory of Molecular Animal Nutrition (Zhejiang University), Ministry of Education, Hangzhou 310058, China.

出版信息

Cells. 2020 Dec 4;9(12):2599. doi: 10.3390/cells9122599.

Abstract

Liver kinase B1 (LKB1) plays important and various roles in the differentiation and lipid metabolism of adipocytes. However, the current knowledge of the respective roles of LKB1 in subcutaneous fat (SCF) and intramuscular fat (IMF) adipocytes remains unclear. This study aimed to discover the different regulatory mechanisms of LKB1 in SCF and IMF adipocytes. We found that LKB1 overexpression inhibited adipogenesis in both SCF and IMF adipocytes, and SCF adipocytes were more sensitive to regulation by LKB1. Transcriptomics results showed that IMF adipocytes had many more differentially expressed genes (DEGs) than SCF adipocytes. Pathway analysis of the shared and distinct DEGs revealed that the main adipogenesis mechanism was similar between SCF and IMF adipocytes upon LKB1 overexpression, while regulatory and metabolic signaling pathways, such as MAPK, PPAR signaling pathways, were differently regulated by LKB1. Several cytokine-related pathways were only enriched in LKB1-overexpressing IMF adipocytes. Our study reveals different regulators and signaling pathways between SCF and IMF adipocytes under LKB1 overexpression, which may be potential targets to differentially control SCF and IMF deposition and improve our understanding of the regulatory mechanisms of IMF deposition.

摘要

肝激酶 B1(LKB1)在脂肪细胞的分化和脂代谢中发挥着重要而多样的作用。然而,目前对于 LKB1 在皮下脂肪(SCF)和肌内脂肪(IMF)脂肪细胞中的各自作用的了解仍不清楚。本研究旨在探索 LKB1 在 SCF 和 IMF 脂肪细胞中的不同调节机制。我们发现,LKB1 的过表达抑制了 SCF 和 IMF 脂肪细胞中的脂肪生成,而 SCF 脂肪细胞对 LKB1 的调节更为敏感。转录组学结果表明,IMF 脂肪细胞的差异表达基因(DEGs)比 SCF 脂肪细胞多得多。对共享和独特的 DEGs 的通路分析表明,在 LKB1 过表达时,SCF 和 IMF 脂肪细胞的主要脂肪生成机制相似,而 LKB1 对 MAPK、PPAR 信号通路等调节和代谢信号通路的调节则不同。一些细胞因子相关通路仅在 LKB1 过表达的 IMF 脂肪细胞中富集。本研究揭示了 LKB1 过表达时 SCF 和 IMF 脂肪细胞之间的不同调节因子和信号通路,这可能是差异化控制 SCF 和 IMF 沉积的潜在靶点,并增进了我们对 IMF 沉积调节机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5dc/7761942/8a5340c26a34/cells-09-02599-g001.jpg

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