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Modulation of the inflammatory response to LPS by the recruitment and activation of brown and brite adipocytes in mice.
American Journal of Physiology-Endocrinology and Metabolism ( IF 5.1 ) Pub Date : 2020-09-21 , DOI: 10.1152/ajpendo.00279.2020
Patrick Munro 1 , Océane Dufies 1 , Samah Rekima 2 , Agnès Loubat 2 , Christophe Duranton 3 , Laurent Boyer 1 , Didier F Pisani 3
Affiliation  

Objectives. Numerous studies have shown that the recruitment and activation of thermogenic adipocytes, which are brown and beige/brite, reduces the mass of adipose tissue and normalizes abnormal glycaemia and lipidaemia. However, the impact of these adipocytes on the inflammatory state of adipose tissue is still not well understood, especially in response to endotoxaemia, which is a major aspect of obesity and metabolic diseases. Methods. First, we analysed the phenotype and metabolic function of white and brite primary adipocytes in response to lipopolysaccharide (LPS) treatment in vitro. Then, 8-week-old male BALB/c mice were treated for one week with a β3-adrenergic receptor agonist (CL316,243, 1 mg/kg/day) to induce recruitment and activation of brown and brite adipocytes and were subsequently injected with LPS (E. coli lipopolysaccharide, i.p., 100 μg/mouse) to generate acute endotoxaemia. The metabolic and inflammatory parameters of the mice were analysed 6 hours later. Results. Our results showed that in response to LPS, thermogenic activity promoted a local anti-inflammatory environment with high secretion of IL-1RA without affecting other anti- or pro-inflammatory cytokines. Interestingly, activation of brite adipocytes reduced the LPS-induced secretion of leptin. However, thermogenic activity and adipocyte function were not altered by LPS treatment in vitro or by acute endotoxaemia in vivo. Conclusion. In conclusion, these results suggest an IL-1RA-mediated immunomodulatory activity of thermogenic adipocytes specifically in response to endotoxaemia. This encourages potential therapy involving brown and brite adipocytes for the treatment of obesity and associated metabolic diseases.

中文翻译:

通过募集和激活小鼠棕色和棕色脂肪细胞对LPS的炎症反应进行调节。

目标。大量研究表明,褐色和米色/棕褐色的产热脂肪细胞的募集和激活,可减少脂肪组织的质量并使正常的血糖和血脂异常正常化。然而,这些脂肪细胞对脂肪组织的炎症状态的影响仍未得到很好的理解,特别是对内毒素血症的反应,内毒素血症是肥胖症和代谢疾病的一个主要方面。方法。首先,我们分析了在体外对脂多糖(LPS)处理后白色和蓝色原代脂肪细胞的表型和代谢功能。然后,将8周大的雄性BALB / c小鼠用β3-肾上腺素能受体激动剂(CL316,243,1 mg / kg / day)治疗一周,以诱导棕色和棕色脂肪细胞的募集和激活,随后进行注射与LPS(大肠杆菌脂多糖,ip ,100μg/小鼠)以产生急性内毒素血症。6小时后分析小鼠的代谢和炎性参数。结果。我们的结果表明,对LPS的反应是,产热活性促进了IL-1RA高分泌的局部抗炎环境,而不影响其他抗炎或促炎细胞因子。有趣的是,英国血脂肪细胞的激活减少了LPS诱导的瘦素分泌。但是,体外LPS处理或体内急性内毒素血症均不会改变产热活性和脂肪细胞功能。结论。总之,这些结果表明,IL-1RA介导的产热脂肪细胞的免疫调节活性专门针对内毒素血症。这鼓励了涉及褐色和棕色脂肪细胞的潜在疗法,用于治疗肥胖症和相关的代谢性疾病。
更新日期:2020-09-22
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