硬脂酰辅酶a去饱和酶1调节小鼠血管周围脂肪组织对高脂肪饮食的代谢和炎症反应

IF 4.5 2区 生物学 Q2 CELL BIOLOGY
Adrian Sowka, Volodymyr V. Balatskyi, Viktor O. Navrulin, James M. Ntambi, Pawel Dobrzyn
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引用次数: 0

摘要

血管周围脂肪组织(PVAT)的失调是肥胖引起血管功能障碍的关键因素。小鼠主动脉周围脂肪组织分为胸血管周围脂肪组织(TPVAT)和腹血管周围脂肪组织(APVAT)两部分。这两部分具有不同的生理特性,在代谢综合征发病时对血管壁的影响也不同。硬脂酰辅酶a去饱和酶1 (SCD1)是一种参与单不饱和脂肪酸合成的酶,已被证明在代谢综合征(包括血管稳态)中起重要作用。尽管对SCD1在血管疾病发展中的作用有相当多的关注,但目前对SCD1与PVAT之间的关系缺乏了解。本研究研究了高脂饮食(HFD)喂养条件下SCD1缺乏对小鼠TPVAT和APVAT脂肪分解、β-氧化、线粒体动力学和炎症的影响。与野生型血管周围脂肪细胞相比,我们发现SCD1 - / -小鼠体内和体外的PVAT中甘油三酯水平较低,这是由于激活的脂肪分解和β-氧化。此外,与野生型小鼠相比,hfd喂养的SCD1 - / -小鼠的PVAT表现为更高水平的氧化磷酸化复合物、线粒体呼吸电位和线粒体形态的改变。此外,HFD诱导的SCD1 - / -小鼠的TPVAT和APVAT表现出更大的促炎巨噬细胞极化和更高的炎症标志物。这可能与游离脂肪酸和二酰基甘油的积累有关,它们富含饱和脂肪酸。这些发现阐明了SCD1在维持血管完整性中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Stearoyl-CoA Desaturase 1 Regulates Metabolism and Inflammation in Mouse Perivascular Adipose Tissue in Response to a High-Fat Diet

The dysregulation of perivascular adipose tissue (PVAT) is a key contributor to obesity-induced vascular dysfunction. Mouse periaortic adipose tissue is divided into two parts: thoracic perivascular adipose tissue (TPVAT) and abdominal perivascular adipose tissue (APVAT). These two parts have different physiological properties, which translate into different effects on the vascular wall in the onset of metabolic syndrome. Stearoyl-CoA desaturase 1 (SCD1) is an enzyme that is involved in the synthesis of monounsaturated fatty acids and has been shown to play an important role in metabolic syndrome, including vascular homeostasis. Despite a considerable focus on the role of SCD1 in the development of vascular disorders, there is currently a lack of knowledge of the relationship between SCD1 and PVAT. The present study investigated effects of SCD1 deficiency on lipolysis, β-oxidation, mitochondrial dynamics, and inflammation in mouse TPVAT and APVAT under high-fat diet (HFD) feeding conditions. We found lower triglyceride levels in PVAT in SCD1−/− mice both in vitro and in vivo compared with wildtype perivascular adipocytes, attributable to activated lipolysis and β-oxidation. Moreover, PVAT in HFD-fed SCD1−/− mice was characterized by higher levels of oxidative phosphorylation complexes and mitochondrial respiratory potential and alterations of mitochondrial morphology compared with wildtype mice. Furthermore, TPVAT and APVAT in SCD1−/− mice showed signs of greater pro-inflammatory macrophage polarization and higher inflammatory markers that were induced by a HFD. This may be related to the accumulation free fatty acids and diacylglycerols, which are enriched in saturated fatty acids. These findings elucidate the role of SCD1 in maintaining vascular integrity.

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来源期刊
CiteScore
14.70
自引率
0.00%
发文量
256
审稿时长
1 months
期刊介绍: The Journal of Cellular Physiology publishes reports of high biological significance in areas of eukaryotic cell biology and physiology, focusing on those articles that adopt a molecular mechanistic approach to investigate cell structure and function. There is appreciation for the application of cellular, biochemical, molecular and in vivo genetic approaches, as well as the power of genomics, proteomics, bioinformatics and systems biology. In particular, the Journal encourages submission of high-interest papers investigating the genetic and epigenetic regulation of proliferation and phenotype as well as cell fate and lineage commitment by growth factors, cytokines and their cognate receptors and signal transduction pathways that influence the expression, integration and activities of these physiological mediators. Similarly, the Journal encourages submission of manuscripts exploring the regulation of growth and differentiation by cell adhesion molecules in addition to the interplay between these processes and those induced by growth factors and cytokines. Studies on the genes and processes that regulate cell cycle progression and phase transition in eukaryotic cells, and the mechanisms that determine whether cells enter quiescence, proliferate or undergo apoptosis are also welcomed. Submission of papers that address contributions of the extracellular matrix to cellular phenotypes and physiological control as well as regulatory mechanisms governing fertilization, embryogenesis, gametogenesis, cell fate, lineage commitment, differentiation, development and dynamic parameters of cell motility are encouraged. Finally, the investigation of stem cells and changes that differentiate cancer cells from normal cells including studies on the properties and functions of oncogenes and tumor suppressor genes will remain as one of the major interests of the Journal.
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