Effect of hepatocyte fatty degeneration induced by free fatty acid on macrophage polarization

Xiaoyun LI; Xixi NI; Jing HUA

doi:10.3969/j.issn.1001-5256.2021.02.027

Volume 37 Issue 2

Mar. 2021

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Article Navigation > Journal of Clinical Hepatology > 2021 > 37(2): 385-389

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Effect of hepatocyte fatty degeneration induced by free fatty acid on macrophage polarization

DOI: 10.3969/j.issn.1001-5256.2021.02.027

Department of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China

Received Date: 2020-08-27
Accepted Date: 2020-10-21
Published Date: 2021-02-20

Abstract

Abstract

Objective To investigate the effect of hepatocyte fatty degeneration induced by free fatty acid on macrophage polarization and the possible mechanism. Methods Primary hepatocytes of C57BL/6 mice were isolated by in situ collagenase perfusion, and then the hepatocytes were divided into control (NC) group and mixed free fatty acid (FFA) treatment group. A conditioned medium (CM) was prepared for hepatocytes and was used for the intervention of RAW264.7 macrophages. Oil red O staining was used to observe lipid deposition in hepatocytes; real-time PCR was used to measure the mRNA expression of lipid metabolism genes and macrophage M1/M2 polarization markers; ELISA was used to measure the levels of cytokines in supernatant; Western blot was used to measure the expression of proteins involved in the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway in macrophages. The independent samples t-test was used for comparison between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the Tukey test was used for further comparison between two groups. Results Compared with the NC group, the FFA treatment group had the deposition of massive lipid droplets in hepatocytes and significant increases in triglyceride and total cholesterol (t=15.65 and 3.49, both P < 0.05). Besides, FFA significantly increased the mRNA expression of the lipid synthesis genes SREBP1C and FASN (t=2.89 and 2.82, both P < 0.05) and reduced the mRNA expression of the lipid decomposition genes ACOX1 and CPT1A (t=14.30 and 3.36, both P < 0.05) in hepatocytes. FFA also induced significant increases in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β, and tumor necrosis factor-α (TNF-α) in supernatant (all P < 0.05). Compared with the CM-NC group, the CM-FFA group had significant increases in the mRNA expression of the M1 phenotype markers iNOS2, TNF-α, and IL-6 (all P < 0.05) and a significant reduction in the mRNA expression of the M2 phenotype marker interleukin-10 (P < 0.05). Moreover, Western blot showed that CM-FFA significantly upregulated the protein expression of TLR4, p-NF-κBp65, and p-ⅠκBα in macrophages (t=2.88, 3.69, and 3.54, all P < 0.05). Conclusion FFA-induced hepatocyte fatty degeneration and inflammation can promote M1 macrophage polarization, thereby initiating and triggering the development and progression of nonalcoholic fatty liver disease.
- Non-alcoholic Fatty Liver Disease,
- Macrophages,
- Fatty Acids

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References(13)

References

[1]	YOUNOSSI ZM. Non-alcoholic fatty liver disease - A global public health perspective[J]. J Hepatol, 2019, 70(3): 531-544. DOI: 10.1016/j.jhep.2018.10.033
[2]	TACKE F. Targeting hepatic macrophages to treat liver diseases[J]. J Hepatol, 2017, 66(6): 1300-1312. DOI: 10.1016/j.jhep.2017.02.026
[3]	WANG Q, XU QY, WU HM, et al. Effect of lipid-induced macrophage M1/M2 polarization on lipid metabolism in hepatocytes[J]. Chin J Hepatol, 2018, 26(4): 276-281. (in Chinese) DOI: 10.3760/cma.j.issn.1007-3418.2018.04.009 王祺, 许钦瑜, 吴惠敏, 等.脂质诱导的巨噬细胞M1/M2型极化对肝细胞脂质代谢的影响[J].中华肝脏病杂志, 2018, 26(4): 276-281. DOI: 10.3760/cma.j.issn.1007-3418.2018.04.009
[4]	GÓMEZ-LECHÓN MJ, DONATO MT, MARTÍNEZ-ROMERO A, et al. A human hepatocellular in vitro model to investigate steatosis[J]. Chem Biol Interact, 2007, 165(2): 106-116. DOI: 10.1016/j.cbi.2006.11.004
[5]	XIAO WS, LE YY, ZENG SL, et al. Research advances in the pathogenesis of nonalcoholic fatty liver disease[J]. J Clin Hepatol, 2020, 36(8): 1874-1879. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.08.043 肖伟松, 乐滢玉, 曾胜澜, 等.非酒精性脂肪性肝病的发病机制研究进展[J].临床肝胆病杂志, 2020, 36(8): 1874-1879. DOI: 10.3969/j.issn.1001-5256.2020.08.043
[6]	HOLLAND WL, BIKMAN BT, WANG LP, et al. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice[J]. J Clin Invest, 2011, 121(5): 1858-1870. DOI: 10.1172/JCI43378
[7]	KAZANKOV K, JØRGENSEN S, THOMSEN KL, et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(3): 145-159. DOI: 10.1038/s41575-018-0082-x
[8]	TOSELLO-TRAMPONT AC, LANDES SG, NGUYEN V, et al. Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-α production[J]. J Biol Chem, 2012, 287(48): 40161-40172. DOI: 10.1074/jbc.M112.417014
[9]	WU HM, NI XX, XU QY, et al. Regulation of lipid-induced macrophage polarization through modulating peroxisome proliferator-activated receptor-gamma activity affects hepatic lipid metabolism via a Toll-like receptor 4/NF-κB signaling pathway[J]. J Gastroenterol Hepatol, 2020, 35(11): 1998-2008. DOI: 10.1111/jgh.15025
[10]	KOU XN, XIE XK, HAO MX, et al. Effects and mechanism of microRNA-140 inhibition on the development of non-alcoholic fatty liver disease in mice[J/CD]. Chin J Liver Dis (Electronic Version), 2020, 12(3): 34-40. (in Chinese) 寇小妮, 解新科, 郝明霞, 等.微小RNA-140抑制对小鼠非酒精性脂肪性肝病进展的影响及机制[J/CD].中国肝脏病杂志(电子版), 2020, 12(3): 34-40.
[11]	ZHENG Y, WANG JR, LIU LL, et al. Molecular mechanism of the anti -liver fibrosis effect of curcumol: An analysis based on the TLR4 /NF-κB signaling pathway[J]. J Clin Hepatol, 2020, 36(7): 1508-1513. (in Chinese) DOI: 10.3969/j.issn.1001-5256.2020.07.013 郑洋, 王嘉孺, 刘露露, 等.基于Toll样受体4 /核因子-κB信号通路研究莪术醇抗肝纤维化的分子机制[J].临床肝胆病杂志, 2020, 36(7): 1508-1513. DOI: 10.3969/j.issn.1001-5256.2020.07.013
[12]	ZHANG CH, LI Y, LI ZY, et al. Protective effect of procyanidine B1 on LPS-induced injury of mouse macrophages RAW264.7 and its mechanism[J]. J Jilin Univ(Med Edit), 2019, 45(6): 1243-1247. (in Chinese) http://www.cnki.com.cn/Article/CJFDTotal-BQEB201906008.htm 张宸豪, 李瑶, 李正祎, 等.原花青素B1对LPS诱导小鼠巨噬细胞RAW264.7损伤的保护作用及其机制[J].吉林大学学报(医学版), 2019, 45(6): 1243-1247. http://www.cnki.com.cn/Article/CJFDTotal-BQEB201906008.htm
[13]	GORDON S, MARTINEZ F O. Alternative activation of macrophages: Mechanism and functions[J]. Immunity, 2010, 32(5): 593-604. DOI: 10.1016/j.immuni.2010.05.007

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Effect of hepatocyte fatty degeneration induced by free fatty acid on macrophage polarization

DOI: 10.3969/j.issn.1001-5256.2021.02.027