AMELIORATING EFFECTS OF CURCUMIN ON HEPATIC STEATOSIS IN HIGH FAT DIET FED MICE

GU Yin-yin; Gusonghan MAITINIYAZI; XIA Shu-fang

Acta Nutrimenta Sinica ›› 2024, Vol. 46 ›› Issue (1) : 48-55.

ORIGINAL ARTICLES

GU Yin-yin¹, Gusonghan MAITINIYAZI², XIA Shu-fang²

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Abstract

Objective To study the effects of curcumin on expressions of hepatic Nrf2/Keap1-targeted microRNAs and Nrf2/Keap1, redox status, and lipid metabolism in high fat diet fed mice. Methods Twenty-four male C57BL/6J mice were randomly divided into three groups: normal control (NC) group, high fat (HF) diet fed group, high fat and curcumin (Cur) group. The mice from the Cur group were fed a high fat diet and received curcumin treatment at the dose of 200 mg/(kg·d) by oral gavage. Twelve weeks later, hepatic histology, expressions of hepatic miRs that targeted on Nrf2/Keap1, and genes in the Nrf2 signaling pathway and lipid metabolism, as well as the oxidative stress biomarkers were determined. Results Compared with the HF group, curcumin effectively improved plasma lipid profiles and inhibited hepatic fat accumulation possibly by down-regulating miR-28, miR-27a and miR-34a and up-regulating miR-200a, resulting in enhanced Nrf2 nuclear translocation and up-regulation of NQO1 and HO-1. Additionally, hepatic GPx, SOD, and CAT activities and GSH level were significantly higher in the Cur group than those in the HF group, while MDA level was remarkably lower. Curcumin also down-regulated the expressions of lipogenesis genes PPARγ and C/EBPα, and up-regulated the expressions of fatty acid oxidation genes PPARα and CPT1α. Conclusion Curcumin can prevent high fat diet induced non-alcoholic fatty liver disease by maintaining hepatic redox status and lipid metabolism via miR/Nrf2 signaling pathway.

Key words

nonalcoholic fatty liver disease / curcumin / microRNA / Nrf2 / lipid metabolism

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GU Yin-yin, Gusonghan MAITINIYAZI, XIA Shu-fang. AMELIORATING EFFECTS OF CURCUMIN ON HEPATIC STEATOSIS IN HIGH FAT DIET FED MICE[J]. Acta Nutrimenta Sinica. 2024, 46(1): 48-55

References

[1] Wong VWS, Chan WK, Chitturi S, et al. Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease Guidelines 2017—Part 1: Definition, risk factors and assessment[J]. J Gastroenterol Hepatol, 2018, 33:70–85.
[2] Zhang C, Yang M.Current options and future directions for NAFLD and NASH treatment[J]. Int J Mol Sci,2021, 22:7571.
[3] El-Agroudy NN, Kurzbach A, Rodionov RN, et al. Are lifestyle therapies effective for NAFLD trea-tment?[J].Trends Endocrinol Metab,2019,30:701–709.
[4] Friedman SL, Neuschwander-Tetri BA, Rinella M, et al. Mechanisms of NAFLD development and thera-peutic strategies[J]. Nat Med, 2018, 24:908–922.
[5] Yu D, Chen G, Pan M, et al. High fat diet-induced oxidative stress blocks hepatocyte nuclear factor 4α and leads to hepatic steatosis in mice[J]. J Cell Physiol, 2018, 233:4770–4782.
[6] Upadhyay KK, Jadeja RN, Vyas HS, et al. Carbon monoxide releasing molecule-A1 improves nonalco-holic steatohepatitis via Nrf2 activation medi- ated improvement in oxidative stress and mito- chondrial function[J]. Redox Biol, 2020, 28:101314.
[7] Li L, Fu J, Liu D, et al. Hepatocyte-specific Nrf2 deficiency mitigates high-fat diet-induced hepatic steatosis:Involvement of reduced PPARγ expression[J]. Redox Biol,2020,30:101412.
[8] Han JH, Park MH and Myung CS. Garcinia cambogia ameliorates non-alcoholic fatty liver disease by inhibiting oxidative stress-mediated steatosis and apoptosis through NRF2-ARE activation[J]. Antioxidants,2021,10:1226.
[9] Abd El-Hameed NM, Abd El-Aleem SA, Khattab MA, et al. Curcumin activation of nuclear factor E2-related factor 2 gene (Nrf2)：prophylactic and therapeutic effect in nonalcoholic steatohepa-titis (NASH)[J].Life Sci,2021,285：119983.
[10] Gjorgjieva M, Sobolewski C, Dolicka D, et al. miRNAs and NAFLD: from pathophysiology to therapy[J].Gut,2019,68:2065–2079.
[11] Paul S, Vázquez LAB, Uribe SP, et al. Roles of microRNAs in carbohydrate and lipid metabolism disorders and their therapeutic potential[J]. Biochim Open,2021,187:83–93.
[12] Nidhi BA, Seema J, Nitin K, et al. Modulation of pentylenetetrazole-induced kindling and oxidative stress by curcumin in mice[J]. Phytomedicine,2011, 18:756–759.
[13] Galicia-Moreno M, Lucano-Landeros S, Monroy-Ramirez HC, et al. Roles of Nrf2 in liver dise-ases:molecular, pharmacological, and epigenetic aspects[J].Antioxidants,2020,9:980.
[14] Ashrafizadeh M, Ahmadi Z, Mohammadinejad R, et al. Curcumin activates the Nrf2 pathway and induces cellular protection against oxidative injury[J]. Curr Mol Med,2020,20:116–133.
[15] Jazayeri-Tehrani SA, Rezayat SM, Mansouri S, et al. Nano-curcumin improves glucose indices, lipids, inflammation, and Nesfatin in overweight and obese patients with non-alcoholic fatty liver disease (NAFLD):a double-blind randomized place- bocontrolled clinical trial[J].Nutr Metab,2019, 16:8.
[16] Zingg JM, Hasan ST and Meydani M. Molecular mechanisms of hypolipidemic effects of curcumin[J]. BioFactors,2013,39:101–121.
[17] Zhong CC, Zhao T, Hogstrand C, et al. Copper (Cu) induced changes of lipid metabolism through oxidative stress-mediated autophagy and Nrf2/ PPARγ pathways[J]. J Nutr Biochem,2022,100:108883.
[18] Kim BR, Lee GY, Yu H, et al. Suppression of Nrf2 attenuates adipogenesis and decreases FGF21 expression through PPAR gamma in 3T3-L1 cells[J]. Biochem Biophys Res Commun, 2018, 497:1149–1153.
[19] Zhao XJ, Yu HW, Yang YZ, et al. Polydatin prevents fructose induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway[J]. Redox Biol, 2018, 18:124–137.
[20] Su RY, Tai WY, Yin HS, et al. miR-432 exerts a protective effect against myocardial ischemia/ reperfusion injury by activating the β-catenin/ HIF-1α pathway and augmenting NRF2-mediated anti-oxidative stress[J]. Am J Transl Res, 2023, 15:392–406.
[21] Zhang C, Kong X, Ma D. miR-141-3p inhibits vascular smooth muscle cell proliferation and migration via regulating Keap1/Nrf2/HO‐1 pathway[J].IUBMB Life,2020,72:2167–2179.
[22] Zimta AA, Cenariu D, Irimie A, et al. The Role of Nrf2 activity in cancer development and progres- sion[J].Cancers,2019,11:E1755.
[23] Wang L, Bayanbold K, Zhao L, et al. Redox sensi-tive miR-27a/b/Nrf2 signaling in Cr(VI)-induced carcinogenesis[J]. Sci Total Environ, 2022, 809:151118.
[24] Teimouri M, Hosseini H, Shabani M, et al. Inhibiting miR-27a and miR-142-5p attenuate nonalcoholic fatty liver disease by regulating Nrf2 signaling pathway[J]. IUBMB Life, 2020, 72:361–372.
[25] Li L, Huang Y, Zhang Z.Expression profile of miRNAs involved in the hepatoprotective effects of curcumin against oxidative stress in Nile tilapia[J]. Aquat Toxicol,2021,237:105896.
[26] Zhang M, Sun W, Zhou M, et al. MicroRNA-27a regulates hepatic lipid metabolism and alleviates NAFLD via repressing FAS and SCD1[J]. Sci Rep, 2017,7:14493.
[27] Li N, Muthusamy S, Liang R, et al. Increased expression of miR-34a and miR-93 in rat liver during aging, and their impact on the expression of Mgst1 and Sirt1[J]. Mech Ageing Dev, 2011, 132:75–85.
[28] Ding J, Li M, Wan X, et al. Effect of miR-34a in regulating steatosis by targeting PPARα expres- sion in nonalcoholic fatty liver disease[J]. Sci Rep,2015, 5:13729.