Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: 20-hydroxyeicosatetraenoic acid; Fatty acids; human adipose stem cells.
2020 Annals of Translational Medicine. All rights reserved.