Structured triglyceride attenuates lung injury and inflammation in lipopolysaccharide‑induced acute lung injury by enhancing GPR120 expression

Sun,Haiyun; Pang,Yanmin; Zhao,Dan; Li,Wenyao

doi:10.3892/mmr.2021.12098

Structured triglyceride attenuates lung injury and inflammation in lipopolysaccharide‑induced acute lung injury by enhancing GPR120 expression

Authors:
- Haiyun Sun
- Yanmin Pang
- Dan Zhao
- Wenyao Li
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Affiliations: Department of Intensive Care Unit, Heze Municipal Hospital, Heze, Shandong 274031, P.R. China
Published online on: April 16, 2021 https://doi.org/10.3892/mmr.2021.12098
Article Number: 459

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Abstract

Acute lung injury (ALI) is a serious clinical problem. The present study was performed to investigate the effect of structured triglyceride (STG) on the development of lipopolysaccharide (LPS)‑induced ALI and its underlying mechanism of action. To establish an LPS‑induced ALI mouse model, mice were intranasally administered 50 µl LPS. The pathological changes in the lung were observed via haematoxylin‑eosin staining. The lung injury score, lung wet/dry weight (W/D) ratio, and myeloperoxidase (MPO) activity were used to evaluate the degree of lung injury. The expression levels of interleukin (IL)‑1β, IL‑6 and tumour necrosis factor‑α in lung tissues were measured through reverse transcription‑quantitative polymerase chain reaction. The enzyme‑linked immunosorbent assay was used to measure the levels of pro‑inflammatory cytokines in bronchoalveolar lavage fluid. Furthermore, western blotting was performed to detect the activity of the transforming growth factor‑α‑activated kinase 1 (TAK1)/NF‑κB pathway. LPS‑induced ALI mice were treated with AH7614 [a G‑protein coupled receptor 120 (GPR120) inhibitor] to confirm the effect of STG on GPR120. STG treatment decreased the lung pathological changes, lung injury score, lung W/D ratio, and proinflammatory cytokine expression levels and inhibited TAK1/NF‑κB pathway activity in the LPS‑induced ALI mouse model. Additionally, AH7614 reversed the inhibitory effects of STG on lung injury, inflammation, and TAK1/NF‑κB pathway activity in ALI. Moreover, AH7614 weakened the inhibitory effects of STG on inflammation and TAK1/NF‑κB pathway activity in LPS‑induced RAW264.7 cells. Collectively, STG may suppress the TAK1/NF‑κB pathway activity by enhancing GPR120 expression to alleviate the lung injury and inflammation in ALI. These results suggest the therapeutic potential of STG in the treatment of ALI.

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1	Bhargava M and Wendt CH: Biomarkers in acute lung injury. Transl Res. 159:205–217. 2012. View Article : Google Scholar : PubMed/NCBI
2	Butt Y, Kurdowska AK and Allen TC: Acute lung injury: A clinical and molecular review. Arch Pathol Lab Med. 140:345–350. 2016. View Article : Google Scholar : PubMed/NCBI
3	Elicker BM, Jones KT, Naeger DM and Frank JA: Imaging of acute lung injury. Radiol Clin North Am. 54:1119–1132. 2016. View Article : Google Scholar : PubMed/NCBI
4	Mowery NT, Terzian WTH and Nelson AC: Acute lung injury. Curr Probl Surg. 57:1007772020. View Article : Google Scholar : PubMed/NCBI
5	Janz DR and Ware LB: Biomarkers of ALI/ARDS: Pathogenesis, discovery, and relevance to clinical trials. Semin Respir Crit Care Med. 34:537–548. 2013. View Article : Google Scholar : PubMed/NCBI
6	Lekka ME, Liokatis S, Nathanail C, Galani V and Nakos G: The impact of IV fat emulsion administration in acute lung injury. Nutr Clin Pract. 19:531–532. 2004. View Article : Google Scholar
7	Shih JM, Shih YM, Pai MH, Hou YC, Yeh CL and Yeh SL: Fish oil-based fat emulsion reduces acute kidney injury and inflammatory response in antibiotic-treated polymicrobial septic mice. Nutrients. 8:1652016. View Article : Google Scholar : PubMed/NCBI
8	Schaefer MB, Ott J, Mohr A, Bi MH, Grosz A, Weissmann N, Ishii S, Grimminger F, Seeger W and Mayer K: Immunomodulation by n-3-versus n-6-rich lipid emulsions in murine acute lung injury-role of platelet-activating factor receptor. Crit Care Med. 35:544–554. 2007. View Article : Google Scholar : PubMed/NCBI
9	Lekka ME, Liokatis S, Nathanail C, Galani V and Nakos G: The impact of intravenous fat emulsion administration in acute lung injury. Am J Respir Crit Care Med. 169:638–644. 2004. View Article : Google Scholar : PubMed/NCBI
10	Ishitsuka Y, Moriuchi H, Yang C, Golbidi S, Irikura M and Irie T: Effects of bolus injection of soybean-based fat emulsion and fatty acids on pulmonary gas exchange function. Biol Pharm Bull. 32:500–503. 2009. View Article : Google Scholar : PubMed/NCBI
11	Wu GH, Zaniolo O, Schuster H, Schlotzer E and Pradelli L: Structured triglycerides versus physical mixtures of medium- and long-chain triglycerides for parenteral nutrition in surgical or critically ill adult patients: Systematic review and meta-analysis. Clin Nutr. 36:150–161. 2017. View Article : Google Scholar : PubMed/NCBI
12	Lin M, Yeh SL, Tsou SS, Wang MY and Chen WJ: Effects of parenteral structured lipid emulsion on modulating the inflammatory response in rats undergoing a total gastrectomy. Nutrition. 25:115–121. 2009. View Article : Google Scholar : PubMed/NCBI
13	Das K and Ghosh M: Structured DAG oil ameliorates renal injury in streptozotocin-induced diabetic rats through inhibition of NF-κB and activation of Nrf2 pathway. Food Chem Toxicol. 100:225–238. 2017. View Article : Google Scholar : PubMed/NCBI
14	Marinissen MJ and Gutkind JS: G-protein-coupled receptors and signaling networks: Emerging paradigms. Trends Pharmacol Sci. 22:368–376. 2001. View Article : Google Scholar : PubMed/NCBI
15	Ren Z, Chen L, Wang Y, Wei X, Zeng S, Zheng Y, Gao C and Liu H: Activation of the omega-3 fatty acid receptor GPR120 protects against focal cerebral ischemic injury by preventing inflammation and apoptosis in mice. J Immunol. 202:747–759. 2019. View Article : Google Scholar : PubMed/NCBI
16	Gaspar RC, Veiga CB, Bessi MP, Dátilo MN, Sant'Ana MR, Rodrigues PB, de Moura LP, da Silva ASR, Santos GA, Catharino RR, et al: Unsaturated fatty acids from flaxseed oil and exercise modulate GPR120 but not GPR40 in the liver of obese mice: A new anti-inflammatory approach. J Nutr Biochem. 66:52–62. 2019. View Article : Google Scholar : PubMed/NCBI
17	Wanten GJ and Calder PC: Immune modulation by parenteral lipid emulsions. Am J Clin Nutr. 85:1171–1184. 2007. View Article : Google Scholar : PubMed/NCBI
18	Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM and Olefsky JM: GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 142:687–698. 2010. View Article : Google Scholar : PubMed/NCBI
19	Huang Q, Wang T and Wang HY: Ginsenoside Rb2 enhances the anti-inflammatory effect of ω-3 fatty acid in LPS-stimulated RAW264.7 macrophages by upregulating GPR120 expression. Acta Pharmacol Sin. 38:192–200. 2017. View Article : Google Scholar : PubMed/NCBI
20	Wang Y, Xu CF, Liu YJ, Mao YF, Lv Z, Li SY, Zhu XY and Jiang L: Salidroside attenuates ventilation induced lung injury via SIRT1-dependent inhibition of NLRP3 inflammasome. Cell Physiol Biochem. 42:34–43. 2017. View Article : Google Scholar : PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Lv H, Liu Q, Wen Z, Feng H, Deng X and Ci X: Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis. Redox Biol. 12:311–324. 2017. View Article : Google Scholar : PubMed/NCBI
23	Zhu T, Wang DX, Zhang W, Liao XQ, Guan X, Bo H, Sun JY, Huang NW, He J, Zhang YK, et al: Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB. PLoS One. 8:e564072013. View Article : Google Scholar : PubMed/NCBI
24	Lei J, Wei Y, Song P, Li Y, Zhang T, Feng Q and Xu G: Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress. Eur J Pharmacol. 818:110–114. 2018. View Article : Google Scholar : PubMed/NCBI
25	Zhang HX, Liu SJ, Tang XL, Duan GL, Ni X, Zhu XY, Liu YJ and Wang CN: H2S attenuates LPS-induced acute lung injury by reducing oxidative/nitrative stress and inflammation. Cell Physiol Biochem. 40:1603–1612. 2016. View Article : Google Scholar : PubMed/NCBI
26	Hou S, Ding H, Lv Q, Yin X, Song J, Landén NX and Fan H: Therapeutic effect of intravenous infusion of perfluorocarbon emulsion on LPS-induced acute lung injury in rats. PLoS One. 9:e878262014. View Article : Google Scholar : PubMed/NCBI
27	Jing H, Yao J, Liu X, Fan H, Zhang F, Li Z, Tian X and Zhou Y: Fish-oil emulsion (omega-3 polyunsaturated fatty acids) attenuates acute lung injury induced by intestinal ischemia-reperfusion through adenosine 5′-monophosphate-activated protein kinase-sirtuin1 pathway. J Surg Res. 187:252–261. 2014. View Article : Google Scholar : PubMed/NCBI
28	Piper SN, Röhm KD, Boldt J, Odermatt B, Maleck WH and Suttner SW: Hepatocellular integrity in patients requiring parenteral nutrition: Comparison of structured MCT/LCT vs a standard MCT/LCT emulsion and a LCT emulsion. Eur J Anaesthesiol. 25:557–565. 2008. View Article : Google Scholar : PubMed/NCBI
29	Mizock BA and DeMichele SJ: The acute respiratory distress syndrome: Role of nutritional modulation of inflammation through dietary lipids. Nutr Clin Pract. 19:563–574. 2004. View Article : Google Scholar : PubMed/NCBI
30	Hecker M, Linder T, Ott J, Walmrath HD, Lohmeyer J, Vadász I, Marsh LM, Herold S, Reichert M, Buchbinder A, et al: Immunomodulation by lipid emulsions in pulmonary inflammation: A randomized controlled trial. Crit Care. 19:2262015. View Article : Google Scholar : PubMed/NCBI
31	Zhao Y and Wang C: Meta-analysis of structured triglyceride versus physical mixture medium- and long-chain triglycerides for PN in liver resection patients. Biomed Res Int. 2017:49201342017. View Article : Google Scholar : PubMed/NCBI
32	Kruimel JW, Naber TH, van der Vliet JA, Carneheim C, Katan MB and Jansen JB: Parenteral structured triglyceride emulsion improves nitrogen balance and is cleared faster from the blood in moderately catabolic patients. JPEN J Parenter Enteral Nutr. 25:237–244. 2001. View Article : Google Scholar : PubMed/NCBI
33	Li C, Ni Q, Pei Y, Ren Y and Feng Y: Meta-analysis of the efficacy and safety of structured triglyceride lipid emulsions in parenteral nutrition therapy in China. Clin Nutr. 38:1524–1535. 2019. View Article : Google Scholar : PubMed/NCBI
34	Kim CS, Joo SY, Kim IJ, Choi HI, Bae EH, Kim SW and Ma SK: Anti-apoptotic effect of G-protein-coupled receptor 40 activation on tumor necrosis factor-α-induced injury of rat proximal tubular cells. Int J Mol Sci. 20:33862019. View Article : Google Scholar : PubMed/NCBI
35	Wlodarczyk M, Sobolewska-Włodarczyk A, Cygankiewicz AI, Jacenik D, Krajewska WM, Stec-Michalska K, Piechota-Polańczyk A, Wiśniewska-Jarosińska M and Fichna J: G protein-coupled receptor 55 (GPR55) expresses differently in patients with Crohn's disease and ulcerative colitis. Scand J Gastroenterol. 52:711–715. 2017. View Article : Google Scholar : PubMed/NCBI
36	Lu M and Zhou E: Long noncoding RNA LINC00662-miR-15b-5p mediated GPR120 dysregulation contributes to osteoarthritis. Pathol Int. 70:155–165. 2020. View Article : Google Scholar : PubMed/NCBI
37	Su VY, Chiou SH, Lin CS, Chen WC, Yu WK, Chen YW, Chen CY and Yang KY: Induced pluripotent stem cells reduce neutrophil chemotaxis via activating GRK2 in endotoxin-induced acute lung injury. Respirology. 22:1156–1164. 2017. View Article : Google Scholar : PubMed/NCBI
38	Lee T, Packiriswamy N, Lee E, Lucas PC, Mccabe LR and Parameswaran N: Role of G protein-coupled receptor kinase-6 in Escherichia coli lung infection model in mice. Physiol Genomics. 49:682–689. 2017. View Article : Google Scholar : PubMed/NCBI
39	Huang Z, Guo F, Xia Z, Liang Y, Lei S, Tan Z, Ma L and Fu P: Activation of GPR120 by TUG891 ameliorated cisplatin-induced acute kidney injury via repressing ER stress and apoptosis. Biomed Pharmacother. 126:1100562020. View Article : Google Scholar : PubMed/NCBI
40	Wellhauser L and Belsham DD: Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons. J Neuroinflammation. 11:602014. View Article : Google Scholar : PubMed/NCBI
41	Sakurai H: Targeting of TAK1 in inflammatory disorders and cancer. Trends Pharmacol Sci. 33:522–530. 2012. View Article : Google Scholar : PubMed/NCBI
42	Gao D, Wang R, Li B, Yang Y, Zhai Z and Chen DY: WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway. Cell Mol Life Sci. 66:2573–2584. 2009. View Article : Google Scholar : PubMed/NCBI
43	Wang W, Xia T and Yu X: Wogonin suppresses inflammatory response and maintains intestinal barrier function via TLR4-MyD88-TAK1-mediated NF-κB pathway in vitro. Inflamm Res. 64:423–431. 2015. View Article : Google Scholar : PubMed/NCBI
44	Wang Y, Tu Q, Yan W, Xiao D, Zeng Z, Ouyang Y, Huang L, Cai J, Zeng X, Chen YJ and Liu A: CXC195 suppresses proliferation and inflammatory response in LPS-induced human hepatocellular carcinoma cells via regulating TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway. Biochem Biophys Res Commun. 456:373–379. 2015. View Article : Google Scholar : PubMed/NCBI
45	Yang X, Kume S, Tanaka Y, Isshiki K, Araki S, Chin-Kanasaki M, Sugimoto T, Koya D, Haneda M, Sugaya T, et al: GW501516, a PPARδ agonist, ameliorates tubulointerstitial inflammation in proteinuric kidney disease via inhibition of TAK1-NFκB pathway in mice. PLoS One. 6:e252712011. View Article : Google Scholar : PubMed/NCBI
46	Yang S, Yu Z, Yuan T, Wang L, Wang X, Yang H, Sun L, Wang Y and Du G: Therapeutic effect of methyl salicylate 2-O-β-d-lactoside on LPS-induced acute lung injury by inhibiting TAK1/NF-kappaB phosphorylation and NLRP3 expression. Int Immunopharmacol. 40:219–228. 2016. View Article : Google Scholar : PubMed/NCBI
47	Hara T, Hirasawa A, Ichimura A, Kimura I and Tsujimoto G: Free fatty acid receptors FFAR1 and GPR120 as novel therapeutic targets for metabolic disorders. J Pharm Sci. 100:3594–3601. 2011. View Article : Google Scholar : PubMed/NCBI
48	Baker MA, Nandivada P, Mitchell PD, Fell GL, Pan A, Cho BS, De La Flor DJ, Anez-Bustillos L, Dao DT, Nosé V and Puder M: Omega-3 fatty acids are protective in hepatic ischemia reperfusion injury in the absence of GPR120 signaling. J Pediatr Surg. 54:2392–2397. 2019. View Article : Google Scholar : PubMed/NCBI
49	Chen YL, Lin YP, Sun CK, Huang TH, Yip HK and Chen YT: Extracorporeal shockwave against inflammation mediated by GPR120 receptor in cyclophosphamide-induced rat cystitis model. Mol Med. 24:602018. View Article : Google Scholar : PubMed/NCBI
50	Meng Z, Si CY, Teng S, Yu XH and Li HY: Tanshinone IIA inhibits lipopolysaccharide-induced inflammatory responses through the TLR4/TAK1/NF-κB signaling pathway in vascular smooth muscle cells. Int J Mol Med. 43:1847–1858. 2019.PubMed/NCBI
51	Sun P, Song SZ, Jiang S, Li X, Yao YL, Wu YL, Lian LH and Nan JX: Salidroside regulates inflammatory response in raw 264.7 macrophages via TLR4/TAK1 and ameliorates inflammation in alcohol binge drinking-induced liver injury. Molecules. 21:14902016. View Article : Google Scholar : PubMed/NCBI
52	Yi H, Peng R, Zhang LY, Sun Y, Peng HM, Liu HD, Yu LJ, Li AL, Zhang YJ, Jiang WH and Zhang Z: LincRNA-Gm4419 knockdown ameliorates NF-κB/NLRP3 inflammasome-mediated inflammation in diabetic nephropathy. Cell Death Dis. 8:e25832017. View Article : Google Scholar : PubMed/NCBI
53	Bai Y, Li Z, Liu W, Gao D, Liu M and Zhang P: Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway. Acta Cir Bras. 34:e2019011042019. View Article : Google Scholar : PubMed/NCBI