Xu Li, Schüler Rita, Xu Chenchen, Seebeck Nicole, Markova Mariya, Murahovschi Veronica, Pfeiffer Andreas F H
Department of Endocrinology, Diabetes and Nutrition, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany.
Ann Transl Med. 2020 Dec;8(24):1652. doi: 10.21037/atm-20-7514.
The modulating mechanism of fatty acids on angiotensin-converting enzyme production (ACE) in human adipocytes is still elusive. Diet-induced regulation of the renin angiotensin system is thought to be involved in obesity and hypertension, and several previous studies have used mouse cell lines such as 3T3-L1 to investigate this. This study was carried out in human subcutaneous adipocytes for better understanding of the mechanism.
Human adipose stem cells were isolated from subcutaneous adipose tissue biopsies collected from four patients during bariatric surgery and differentiated into mature adipocytes. The mRNA expression and the activity of ACE were measured under different stimuli in cell cultures.
Arachidonic acid (AA) decreased ACE mRNA expression and ACE activity in a dose-dependent manner while palmitic acid had no effect. The decrease of ACE by 100 µM AA was reversed by the addition of 5 µM nuclear factor-κB (NF-κB) inhibitor. Furthermore, when the production of 20-hydroxyeicosatetraenoic acid, a metabolite of AA, was stopped by the specific inhibitor HET0016 (10 µM) in the culture media, the effect of AA was blocked.
This study indicated that AA can decrease the expression and activity of ACE in cultured human adipocytes, via an inflammatory NF-κB-dependent pathway. Blocking 20-hydroxyeicosatetraenoic acid attenuated the ACE-decreasing effects of AA.
脂肪酸对人脂肪细胞中血管紧张素转换酶生成（ACE）的调节机制仍不清楚。饮食诱导的肾素血管紧张素系统调节被认为与肥胖和高血压有关，此前有多项研究使用3T3-L1等小鼠细胞系对此进行研究。本研究在人皮下脂肪细胞中开展，以更好地了解该机制。
从4例患者在减肥手术期间采集的皮下脂肪组织活检样本中分离出人脂肪干细胞，并将其分化为成熟脂肪细胞。在细胞培养中，于不同刺激条件下测量ACE的mRNA表达和活性。
花生四烯酸（AA）以剂量依赖方式降低ACE的mRNA表达和ACE活性，而棕榈酸无此作用。添加5 μM核因子κB（NF-κB）抑制剂可逆转100 μM AA对ACE的降低作用。此外，当培养基中使用特异性抑制剂HET0016（10 μM）阻断AA的代谢产物20-羟基二十碳四烯酸的生成时，AA的作用被阻断。
本研究表明，AA可通过炎症性NF-κB依赖途径降低培养的人脂肪细胞中ACE的表达和活性。阻断20-羟基二十碳四烯酸可减弱AA对ACE的降低作用。
