Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232-2584, USA.
Obes Res Clin Pract. 2020 Jul-Aug;14(4):333-338. doi: 10.1016/j.orcp.2020.06.002. Epub 2020 Jun 25.
Individuals with non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), are at increased risk for cardiovascular events, independent of traditional risk factors. Limited data on pro-inflammatory high density lipoprotein (HDL) in NASH exists in the literature. We hypothesized that HDL from individuals with NASH would be more pro-inflammatory than HDL from individuals without NASH.
Study participants were individuals with obesity who had undergone bariatric surgery with wedge liver biopsy. Using HDL isolated from serum obtained from study participants at the time of surgery, HDL-elicited macrophage cytokine expression (TNF-α, IL-1β, and IL-6) from THP-1 macrophages, HDL-associated receptor expression (ABCA1 and ABCG1) from apolipoprotein E deficient (apo E) mouse peritoneal macrophages, and isolevuglandin (isoLG) modified HDL were measured.
11 women with NASH and 15 women without NASH were included in the study. Both TNF-α (P = 0.032) and IL-1β (P = 0.029) were significantly more expressed by THP-1 macrophages exposed to HDL from women with NASH compared to women without NASH. ABCA1 and ABCG1 expression by apo E mouse peritoneal macrophages was not significantly different when exposed to HDL from either women with NASH or women without NASH. IsoLG-modified HDL isolated from the serum of women with NASH trended higher than women without NASH.
Our study suggests a more pro-inflammatory HDL in women with obesity and NASH compared to women with obesity and without NASH.
非酒精性脂肪性肝病（NAFLD）患者，包括非酒精性脂肪性肝炎（NASH），心血管事件的风险增加，独立于传统的危险因素。关于 NASH 中促炎的高密度脂蛋白（HDL）的有限数据存在于文献中。我们假设 NASH 患者的 HDL 比没有 NASH 的患者的 HDL 更具有促炎作用。
研究参与者是接受过减肥手术和楔形肝活检的肥胖患者。使用从手术时从研究参与者的血清中分离的 HDL，从 THP-1 巨噬细胞中测量 HDL 引起的巨噬细胞细胞因子表达（TNF-α、IL-1β 和 IL-6）、载脂蛋白 E 缺乏（apoE）小鼠腹腔巨噬细胞中的 HDL 相关受体表达（ABCA1 和 ABCG1）和异亮氨酸加合物修饰的 HDL。
本研究纳入了 11 名 NASH 女性和 15 名非 NASH 女性。与非 NASH 女性相比，THP-1 巨噬细胞暴露于 NASH 女性的 HDL 后，TNF-α（P=0.032）和 IL-1β（P=0.029）的表达明显更高。当暴露于 NASH 女性或非 NASH 女性的 HDL 时，apoE 小鼠腹腔巨噬细胞的 ABCA1 和 ABCG1 表达没有明显差异。从 NASH 女性血清中分离的异亮氨酸加合物修饰的 HDL 高于非 NASH 女性。
与肥胖且没有 NASH 的女性相比，我们的研究表明肥胖且患有 NASH 的女性的 HDL 更具有促炎作用。
