Acacetin Protects Against Non-Alcoholic Fatty Liver Disease by Regulating Lipid Accumulation and Inflammation in Mice

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 May 14

PMID 35563076

Authors

Chian-Jiun Liou

Shu-Ju Wu

Szu-Chuan Shen

Li-Chen Chen

Ya-Ling Chen

Wen-Chung Huang

Affiliations

Soon will be listed here.

Abstract

We previously demonstrated that acacetin reduces adipogenesis in adipocytes, and decreases lipid accumulation in visceral adipocyte tissue. Here we investigated whether acacetin regulated the mechanisms of lipogenesis and inflammation in non-alcoholic fatty liver disease (NAFLD) in obese mice. Male C57BL/6 mice were fed a high-fat diet (HFD), and then administered acacetin by intraperitoneal injection. Acacetin reduced body weight and liver weight in obese mice. Acacetin-treated obese mice exhibited decreased lipid accumulation, increased glycogen accumulation, and improved hepatocyte steatosis. Acacetin regulated triglycerides and total cholesterol in the liver and serum. Acacetin decreased low-density lipoprotein and leptin concentrations, but increased high-density lipoprotein and adiponectin levels in obese mice. Acacetin effectively weakened the gene expressions of transcription factors related to lipogenesis, and promoted the expressions of genes related to lipolysis and fatty acid β-oxidation in liver. Acacetin also reduced expressions of inflammation-related cytokines in the serum and liver. Oleic acid induced lipid accumulation in murine FL83B hepatocytes, and the effects of acacetin treatment indicated that acacetin may regulate lipid metabolism through the AMPK pathway. Acacetin may protect against hepatic steatosis by modulating inflammation and AMPK expression.

Citing Articles

Targeting AMPK related signaling pathways: A feasible approach for natural herbal medicines to intervene non-alcoholic fatty liver disease.

Cai Y, Fang L, Chen F, Zhong P, Zheng X, Xing H J Pharm Anal. 2025; 15(1):101052.

PMID: 40034684 PMC: 11873010. DOI: 10.1016/j.jpha.2024.101052.

Acacetin, a Natural Flavone with Potential in Improving Liver Disease Based on Its Anti-Inflammation, Anti-Cancer, Anti-Infection and Other Effects.

Chen K, Gao Z Molecules. 2024; 29(20).

PMID: 39459239 PMC: 11509893. DOI: 10.3390/molecules29204872.

Buddleoside-rich Chrysanthemum indicum L. extract modulates macrophage-mediated inflammation to prevent metabolic syndrome induced by unhealthy diet.

Zhou Y, Su J, Dong Y, He Z, Wang Y, Chen S BMC Complement Med Ther. 2024; 24(1):315.

PMID: 39179999 PMC: 11344343. DOI: 10.1186/s12906-024-04583-2.

Acacetin targets STING to alleviate the destabilization of the medial meniscus-induced osteoarthritis in mice.

Xu D, Zhang L, Song C, Zhang D, Xing C, Lv J Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(11):8863-8878.

PMID: 38856915 DOI: 10.1007/s00210-024-03167-8.

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective.

Fu Y, Wang Z, Qin H Metabolites. 2024; 14(4).

PMID: 38668346 PMC: 11052500. DOI: 10.3390/metabo14040218.

References

Gluvic Z, Zaric B, Resanovic I, Obradovic M, Mitrovic A, Radak D . Link between Metabolic Syndrome and Insulin Resistance. Curr Vasc Pharmacol. 2016; 15(1):30-39. DOI: 10.2174/1570161114666161007164510. View

Remmerie A, Scott C . Macrophages and lipid metabolism. Cell Immunol. 2018; 330:27-42. PMC: 6108423. DOI: 10.1016/j.cellimm.2018.01.020. View

Kleiner D, Brunt E, Van Natta M, Behling C, Contos M, Cummings O . Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005; 41(6):1313-21. DOI: 10.1002/hep.20701. View

Qin G, Ma J, Huang Q, Yin H, Han J, Li M . Isoquercetin Improves Hepatic Lipid Accumulation by Activating AMPK Pathway and Suppressing TGF-β Signaling on an HFD-Induced Nonalcoholic Fatty Liver Disease Rat Model. Int J Mol Sci. 2018; 19(12). PMC: 6321444. DOI: 10.3390/ijms19124126. View

Huang D, El-Serag H, Loomba R . Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2020; 18(4):223-238. PMC: 8016738. DOI: 10.1038/s41575-020-00381-6. View

Pan M, Lai C, Wang Y, Ho C . Acacetin suppressed LPS-induced up-expression of iNOS and COX-2 in murine macrophages and TPA-induced tumor promotion in mice. Biochem Pharmacol. 2006; 72(10):1293-303. DOI: 10.1016/j.bcp.2006.07.039. View

Abdelmalek M . Nonalcoholic fatty liver disease: another leap forward. Nat Rev Gastroenterol Hepatol. 2021; 18(2):85-86. PMC: 7791336. DOI: 10.1038/s41575-020-00406-0. View

Lee Y, Olefsky J . Chronic tissue inflammation and metabolic disease. Genes Dev. 2021; 35(5-6):307-328. PMC: 7919414. DOI: 10.1101/gad.346312.120. View

Liou C, Lee Y, Ting N, Chen Y, Shen S, Wu S . Protective Effects of Licochalcone A Ameliorates Obesity and Non-Alcoholic Fatty Liver Disease Via Promotion of the Sirt-1/AMPK Pathway in Mice Fed a High-Fat Diet. Cells. 2019; 8(5). PMC: 6562591. DOI: 10.3390/cells8050447. View

10.

Liang C, Li Y, Bai M, Huang Y, Yang H, Liu L . Hypericin attenuates nonalcoholic fatty liver disease and abnormal lipid metabolism via the PKA-mediated AMPK signaling pathway in vitro and in vivo. Pharmacol Res. 2020; 153:104657. DOI: 10.1016/j.phrs.2020.104657. View

11.

Bowers E, Singer K . Obesity-induced inflammation: The impact of the hematopoietic stem cell niche. JCI Insight. 2021; 6(3). PMC: 7934850. DOI: 10.1172/jci.insight.145295. View

12.

Powell E, Wong V, Rinella M . Non-alcoholic fatty liver disease. Lancet. 2021; 397(10290):2212-2224. DOI: 10.1016/S0140-6736(20)32511-3. View

13.

Wang Y, Viscarra J, Kim S, Sul H . Transcriptional regulation of hepatic lipogenesis. Nat Rev Mol Cell Biol. 2015; 16(11):678-89. PMC: 4884795. DOI: 10.1038/nrm4074. View

14.

Liou C, Wu S, Chen L, Yeh K, Chen C, Huang W . Acacetin from Traditionally Used Kar. et Kir. Suppressed Adipogenesis in 3T3-L1 Adipocytes and Attenuated Lipid Accumulation in Obese Mice. Front Pharmacol. 2017; 8:589. PMC: 5581916. DOI: 10.3389/fphar.2017.00589. View

15.

Singh S, Gupta P, Meena A, Luqman S . Acacetin, a flavone with diverse therapeutic potential in cancer, inflammation, infections and other metabolic disorders. Food Chem Toxicol. 2020; 145:111708. DOI: 10.1016/j.fct.2020.111708. View

16.

Tiao M, Lin Y, Yu H, Sheen J, Lin I, Lai Y . Resveratrol ameliorates maternal and post-weaning high-fat diet-induced nonalcoholic fatty liver disease via renin-angiotensin system. Lipids Health Dis. 2018; 17(1):178. PMC: 6064630. DOI: 10.1186/s12944-018-0824-3. View

17.

Liou C, Dai Y, Wang C, Fang L, Huang W . Maslinic acid protects against obesity-induced nonalcoholic fatty liver disease in mice through regulation of the Sirt1/AMPK signaling pathway. FASEB J. 2019; 33(11):11791-11803. PMC: 6902708. DOI: 10.1096/fj.201900413RRR. View

18.

Bu J, Shi S, Wang H, Niu X, Zhao Z, Wu W . Acacetin protects against cerebral ischemia-reperfusion injury the NLRP3 signaling pathway. Neural Regen Res. 2019; 14(4):605-612. PMC: 6352603. DOI: 10.4103/1673-5374.247465. View

19.

Felix D, Costenaro F, Gottschall C, Coral G . Non-alcoholic fatty liver disease (Nafld) in obese children- effect of refined carbohydrates in diet. BMC Pediatr. 2016; 16(1):187. PMC: 5111335. DOI: 10.1186/s12887-016-0726-3. View

20.

Scorletti E, Carr R . A new perspective on NAFLD: Focusing on lipid droplets. J Hepatol. 2021; 76(4):934-945. DOI: 10.1016/j.jhep.2021.11.009. View