{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T14:24:19Z","timestamp":1769523859123,"version":"3.49.0"},"reference-count":78,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the 111 project from the Education Ministry of China","award":["B18053"],"award-info":[{"award-number":["B18053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent liver disease globally. Pea albumin (PA) has demonstrated positive impacts on reducing obesity and improving glucose metabolism. In this research, a mouse model of NAFLD induced by a high-fat diet (HFD) was employed to examine the impact of PA on NAFLD and explore its potential mechanisms. The findings revealed that mice subjected to a HFD developed pronounced fatty liver alterations. The intervention with PA significantly lowered serum TC by 26.81%, TG by 43.55%, and LDL-C by 57.79%. It also elevated HDL-C levels by 1.2 fold and reduced serum ALT by 37.94% and AST by 31.21% in mice fed a HFD. These changes contributed to the reduction in hepatic steatosis and lipid accumulation. Additionally, PA improved insulin resistance and inhibited hepatic oxidative stress and inflammatory responses. Mechanistic studies revealed that PA alleviated lipid accumulation in HFD-induced NAFLD by activating the phosphorylation of AMPK\u03b1 and ACC, inhibiting the expression of SREBF1 and FASN to reduce hepatic lipogenesis, and increasing the expression of ATGL, PPAR\u03b1, and PPAR\u03b3 to promote lipolysis and fatty acid oxidation. These results indicate that PA could serve as a dietary supplement for alleviating NAFLD, offering a theoretical foundation for the rational intake of PA in NAFLD intervention.<\/jats:p>","DOI":"10.3390\/nu16142232","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T11:33:22Z","timestamp":1720697602000},"page":"2232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pea Albumin Extracted from Pea (Pisum sativum L.) Seeds Ameliorates High-Fat-Diet-Induced Non-Alcoholic Fatty Liver Disease by Regulating Lipogenesis and Lipolysis Pathways"],"prefix":"10.3390","volume":"16","author":[{"given":"Shucheng","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"},{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengwu","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7758-5161","authenticated-orcid":false,"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"},{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9975-6737","authenticated-orcid":false,"given":"Pengjie","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Tibet Tianhong Science and Technology Co., Ltd., Lhasa 850000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-3685","authenticated-orcid":false,"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Health, China Agricultural University, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Brunt, E.M., Wong, V.W.S., Nobili, V., Day, C.P., Sookoian, S., Maher, J.J., Bugianesi, E., Sirlin, C.B., Neuschwander-Tetri, B., and Rinella, M.E. (2015). Nonalcoholic fatty liver disease. Nat. Rev. Dis. Primers, 1.","DOI":"10.1038\/nrdp.2015.80"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/joim.13531","article-title":"Current treatment of non-alcoholic fatty liver disease","volume":"292","author":"Paternostro","year":"2022","journal-title":"J. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metab. Clin. Exp."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American association for the study of liver diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1053\/j.gastro.2015.04.014","article-title":"Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients","volume":"149","author":"Lassailly","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"305","DOI":"10.7326\/M15-1774","article-title":"Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: A randomized trial","volume":"165","author":"Cusi","year":"2016","journal-title":"Ann. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yoneda, M., Honda, Y., Ogawa, Y., Kessoku, T., Kobayashi, T., Imajo, K., Ozaki, A., Nogami, A., Taguri, M., and Yamanaka, T. (2021). Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): A randomized prospective open-label controlled trial. BMJ Open Diabetes Res. Care, 9.","DOI":"10.1136\/bmjdrc-2020-001990"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","article-title":"A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis","volume":"384","author":"Newsome","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S0140-6736(15)00803-X","article-title":"Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (lean): A multicentre, double-blind, randomised, placebo-controlled phase 2 study","volume":"387","author":"Armstrong","year":"2016","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1007\/s00394-020-02362-6","article-title":"Betaine prevented high-fat diet-induced NAFLD by regulating the fgf10\/ampk signaling pathway in ApoE\u2212\/\u2212 mice","volume":"60","author":"Chen","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1080\/13880209.2016.1187179","article-title":"Curcumin inhibits hyperlipidemia and hepatic fat accumulation in high-fructose-fed male wistar rats","volume":"54","author":"Maithilikarpagaselvi","year":"2016","journal-title":"Pharm. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1017\/S0007114518000739","article-title":"Soya protein \u03b2-conglycinin ameliorates fatty liver and obesity in diet-induced obese mice through the down-regulation of PPAR\u03b3","volume":"119","author":"Li","year":"2018","journal-title":"Br. J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yan, H., Xia, M., Wang, Y., Chang, X., Yao, X., Rao, S., Zeng, M., Tu, Y., Feng, R., and Jia, W. (2015). Efficacy of berberine in patients with non-alcoholic fatty liver disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134172"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"831","DOI":"10.2174\/1389203722666211202151557","article-title":"Soybean \u03b2-conglycinin: Structure characteristic, allergenicity, plasma lipid-controlling, prevention of obesity and non-alcoholic fatty liver disease","volume":"22","author":"Shan","year":"2021","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1055\/s-0043-100019","article-title":"Efficacy and safety of phytosomal curcumin in non-alcoholic fatty liver disease: A randomized controlled trial","volume":"67","author":"Panahi","year":"2017","journal-title":"Drug Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.jff.2017.05.038","article-title":"A pea (Pisum sativum L.) seed albumin extract prevents colonic dss induced dysbiosis in mice","volume":"35","author":"Ruiz","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/jsfa.6250","article-title":"Characterization of pea (Pisum sativum) seed protein fractions","volume":"94","author":"Rubio","year":"2014","journal-title":"J. Sci. Food Agric."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, S., Jin, W., Zhang, W., Ren, F., Wang, P., and Liu, N. (2022). Pea albumin attenuates dextran sulfate sodium-induced colitis by regulating NF-kappa B signaling and the intestinal microbiota in mice. Nutrients, 14.","DOI":"10.3390\/nu14173611"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Liu, N., Song, Z., Jin, W., Yang, Y., Sun, S., Zhang, Y., Zhang, S., Liu, S., Ren, F., and Wang, P. (2022). Pea albumin extracted from pea (Pisum sativum L.) seed protects mice from high fat diet-induced obesity by modulating lipid metabolism and gut microbiota. J. Funct. Foods, 97.","DOI":"10.1016\/j.jff.2022.105234"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ruiz, R., Olias, R., Clemente, A., and Rubio, L.A. (2020). A pea (Pisum sativum L.) seed vicilins hydrolysate exhibits PPAR\u03b3 ligand activity and modulates adipocyte differentiation in a 3t3-l1 cell culture model. Foods, 9.","DOI":"10.3390\/foods9060793"},{"key":"ref_23","first-page":"67","article-title":"Changes in the content and anti-oxidative activity of polyphenols and albumins in pea during its fermentation in an sssr bioreactor","volume":"15","author":"Miszkiewicz","year":"2008","journal-title":"Zywnosc-Nauka Technol. Jakosc"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.peptides.2008.01.013","article-title":"The effect of pea albumin 1f on glucose metabolism in mice","volume":"29","author":"Dun","year":"2008","journal-title":"Peptides"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Heo, S.W., Chung, K.S., Yoon, Y.S., Kim, S.Y., Ahn, H.S., Shin, Y.K., Lee, S.H., and Lee, K.T. (2023). Standardized ethanol extract of cassia mimosoides var. Nomame makino ameliorates obesity via regulation of adipogenesis and lipogenesis in 3t3-l1 cells and high-fat diet-induced obese mice. Nutrients, 15.","DOI":"10.3390\/nu15030613"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1007\/s00125-022-05851-x","article-title":"Empagliflozin protects mice against diet-induced obesity, insulin resistance and hepatic steatosis","volume":"66","author":"Radlinger","year":"2022","journal-title":"Diabetologia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1021\/acs.jafc.2c08169","article-title":"Millet bran protein hydrolysate displays the anti-non-alcoholic fatty liver disease effect via activating peroxisome proliferator-activated receptor \u03b3 to restrain fatty acid uptake","volume":"71","author":"Shan","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Liu, Z., Patil, I.Y., Jiang, T., Sancheti, H., Walsh, J.P., Stiles, B.L., Yin, F., and Cadenas, E. (2015). High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128274"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zou, Y., Zhong, L., Hu, C., Zhong, M., Peng, N., and Sheng, G. (2021). LDL\/HDL cholesterol ratio is associated with new-onset NAFLD in chinese non-obese people with normal lipids: A 5-year longitudinal cohort study. Lipids Health Dis., 20.","DOI":"10.1186\/s12944-021-01457-1"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bazick, J., Donithan, M., Neuschwander-Tetri, B.A., Kleiner, D.E., Brunt, E., Wilson, L., Doo, E., Lavine, J.E., and Loomba, R. (2014). Clinical model for NASH or advanced fibrosis in patients with diabetes and NAFLD. Gastroenterology, 146.","DOI":"10.1016\/S0016-5085(14)63445-4"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ramanathan, R., Ali, A.H., and Ibdah, J.A. (2022). Mitochondrial dysfunction plays central role in nonalcoholic fatty liver disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137280"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"160","DOI":"10.4103\/2230-8210.146874","article-title":"Assessment of insulin sensitivity\/resistance","volume":"19","author":"Gutch","year":"2015","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11401","DOI":"10.1021\/acs.jafc.2c04406","article-title":"Phytic acid improves hepatic steatosis, inflammation, and oxidative stress in high-fat diet (HFD)-fed mice by modulating the gut\u2013liver axis","volume":"70","author":"Ran","year":"2022","journal-title":"J. Agric. Food. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111732","DOI":"10.1016\/j.foodres.2022.111732","article-title":"Noni (Morinda citrifolia L.) fruit phenolic extract supplementation ameliorates NAFLD by modulating insulin resistance, oxidative stress, inflammation, liver metabolism and gut microbiota","volume":"160","author":"Wang","year":"2022","journal-title":"Food Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhang, J., Zhou, X., Wang, X., Zhang, J., Yang, M., Liu, Y., Cao, J., and Cheng, G. (2022). Que zui tea ameliorates hepatic lipid accumulation and oxidative stress in high fat diet induced nonalcoholic fatty liver disease. Food Res. Int., 156.","DOI":"10.1016\/j.foodres.2022.111196"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/liv.14869","article-title":"Current management of NAFLD\/NASH","volume":"41","author":"Cardoso","year":"2021","journal-title":"Liver Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1021\/acs.jafc.9b06311","article-title":"Selective complex coacervation of pea whey proteins with chitosan to purify main 2s albumins","volume":"68","author":"Yang","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Rom, O., Liu, Y., Liu, Z., Zhao, Y., Wu, J., Ghrayeb, A., Villacorta, L., Fan, Y., Chang, L., and Wang, L. (2020). Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome. Sci. Transl. Med., 12.","DOI":"10.1126\/scitranslmed.aaz2841"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhu, L., Xiao, M., Luo, J., Li, S., Liu, W., Wu, J., and Song, Z. (2023). Polysaccharides from Ostrea rivularis rebuild the balance of gut microbiota to ameliorate non-alcoholic fatty liver disease in ApoE\u2212\/\u2212 mice. Int. J. Biol. Macromol., 235.","DOI":"10.1016\/j.ijbiomac.2023.123853"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zineldeen, D.H., Tahoon, N.M., and Sarhan, N.I. (2023). Aicar ameliorates non-alcoholic fatty liver disease via modulation of the HGF\/NF-\u03baB\/SNARK signaling pathway and restores mitochondrial and endoplasmic reticular impairments in high-fat diet-fed rats. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043367"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1002\/hep.24001","article-title":"Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis","volume":"52","author":"Tilg","year":"2010","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10809","article-title":"Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity","volume":"482","author":"Elinav","year":"2012","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","article-title":"Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease","volume":"75","author":"Ipsen","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1039\/D0FO00206B","article-title":"A lupine (Lupinus angustifolious L.) peptide prevents non-alcoholic fatty liver disease in high-fat-diet-induced obese mice","volume":"11","author":"Toscano","year":"2020","journal-title":"Food Funct."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.3748\/wjg.v25.i24.3009","article-title":"Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease","volume":"25","author":"Mato","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tong, L., Xiao, T., Wang, L., Lu, C., Liu, L., Zhou, X., Wang, A., Qin, W., and Wang, F. (2021). Plant protein reduces serum cholesterol levels in hypercholesterolemia hamsters by modulating the compositions of gut microbiota and metabolites. Iscience, 24.","DOI":"10.21203\/rs.3.rs-142744\/v1"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.14202\/vetworld.2018.1433-1439","article-title":"Supplementation of whole grain flaxseeds (Linum usitatissimum) along with high cholesterol diet and its effect on hyperlipidemia and initiated atherosclerosis in wistar albino male rats","volume":"11","author":"Naik","year":"2018","journal-title":"Vet. World"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1159\/000374037","article-title":"Baicalin attenuates high fat diet-induced obesity and liver dysfunction: Dose-response and potential role of CaMKK\u03b2\/AMPK\/ACC pathway","volume":"35","author":"Xi","year":"2015","journal-title":"Cell Physiol. Biochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1007\/s10620-016-4153-y","article-title":"Lifestyle and dietary interventions in the management of nonalcoholic fatty liver disease","volume":"61","author":"Hannah","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1002\/oby.21890","article-title":"Differential impact of weight loss on nonalcoholic fatty liver resolution in a north American cohort with obesity","volume":"25","author":"Rachakonda","year":"2017","journal-title":"Obesity"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1039\/C9FO03003D","article-title":"The protective mechanism of lactobacillus plantarum fzu3013 against non-alcoholic fatty liver associated with hyperlipidemia in mice fed a high-fat diet","volume":"11","author":"Chen","year":"2020","journal-title":"Food Funct."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Aragones, G., Gonzalez-Garcia, S., Aguilar, C., Richart, C., and Auguet, T. (2019). Gut microbiota-derived mediators as potential markers in nonalcoholic fatty liver disease. BioMed Res. Int., 2019.","DOI":"10.1155\/2019\/8507583"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.plipres.2008.08.001","article-title":"Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD)","volume":"48","author":"Musso","year":"2009","journal-title":"Prog. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ofosu, F.K., Mensah, D.-J.F., Daliri, E.B.-M., and Oh, D.-H. (2021). Exploring molecular insights of cereal peptidic antioxidants in metabolic syndrome prevention. Antioxidants, 10.","DOI":"10.3390\/antiox10040518"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"35298","DOI":"10.1074\/jbc.M405203200","article-title":"Insulin resistance due to phosphorylation of insulin receptor substrate-1 at serine 302","volume":"279","author":"Werner","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.freeradbiomed.2011.10.003","article-title":"Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis","volume":"52","author":"Rolo","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.jhep.2012.05.019","article-title":"Critical role of cytochrome p450 2e1 (cyp2e1) in the development of high fat-induced non-alcoholic steatohepatitis","volume":"57","author":"Abdelmegeed","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Liao, M., Sun, C., Li, R., Li, W., Ge, Z., Adu-Frimpong, M., Xu, X., and Yu, J. (2022). Amelioration action of gastrodigenin rhamno-pyranoside from moringa seeds on non-alcoholic fatty liver disease. Food Chem., 379.","DOI":"10.1016\/j.foodchem.2022.132087"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1021\/acs.jafc.8b02241","article-title":"Salicin from alangium chinense ameliorates rheumatoid arthritis by modulating the Nrf2-HO-1-ROS pathways","volume":"66","author":"Zhai","year":"2018","journal-title":"J. Agric. Food. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Qiu, M., Xiao, F., Wang, T., Piao, S., Zhao, W., Shao, S., Yan, M., and Zhao, D. (2020). Protective effect of hedansanqi tiaozhi tang against non-alcoholic fatty liver disease in vitro and in vivo through activating Nrf2\/HO-1 antioxidant signaling pathway. Phytomedicine, 67.","DOI":"10.1016\/j.phymed.2019.153140"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.molmet.2016.01.010","article-title":"Mitochondrial gene polymorphisms alter hepatic cellular energy metabolism and aggravate diet-induced non-alcoholic steatohepatitis","volume":"5","author":"Schroeder","year":"2016","journal-title":"Mol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1136\/gut.2003.034165","article-title":"Activation of nuclear factor \u03baB in colonic mucosa from patients with collagenous and ulcerative colitis","volume":"54","author":"Andresen","year":"2005","journal-title":"Gut"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhao, H., Gao, X., Liu, Z., Zhang, L., Fang, X., Sun, J., Zhang, Z., and Sun, Y. (2022). Sodium alginate prevents non-alcoholic fatty liver disease by modulating the gut\u2013liver axis in high-fat diet-fed rats. Nutrients, 14.","DOI":"10.3390\/nu14224846"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1016\/j.fshw.2022.04.034","article-title":"Yogurt-derived lactobacillus plantarum q16 alleviated high-fat diet-induced non-alcoholic fatty liver disease in mice","volume":"11","author":"Tang","year":"2022","journal-title":"Food Sci. Hum. Wellness"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1172\/JCI0215593","article-title":"Srebps: Activators of the complete program of cholesterol and fatty acid synthesis in the liver","volume":"109","author":"Horton","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wang, H., Peng, H., Chien, Y., Chen, Y., Lu, N., and Yang, S. (2018). Effects of fish oil on lipid metabolism and its molecular biological regulators in chronic ethanol-fed rats. Nutrients, 10.","DOI":"10.3390\/nu10070802"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nrd1344","article-title":"Amp kinase and malonyl-coa: Targets for therapy of the metabolic syndrome","volume":"3","author":"Ruderman","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.cmet.2011.03.009","article-title":"AMPK phosphorylates and inhibits srebp activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice","volume":"13","author":"Li","year":"2011","journal-title":"Cell Metab."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Yuan, E., Duan, X., Xiang, L., Ren, J., Lai, X., Li, Q., Sun, L., and Sun, S. (2018). Aged oolong tea reduces high-fat diet-induced fat accumulation and dyslipidemia by regulating the AMPK\/ACC signaling pathway. Nutrients, 10.","DOI":"10.3390\/nu10020187"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Woo, K.J., Hong, J., Han, K.I., Kim, H.S., and Kim, T.J. (2023). Heat-killed enterococcus faecalis inhibit fl83b hepatic lipid accumulation and high fat diet-induced fatty liver damage in rats by activating lipolysis through the regulation the AMPK signaling pathway. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054486"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3892\/ijmm.2016.2831","article-title":"Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK\/ACC in high-fat diet-fed mice","volume":"39","author":"Kawaguchi","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/hep.24006","article-title":"Adipose triglyceride lipase is a major hepatic lipase that regulates triacylglycerol turnover and fatty acid signaling and partitioning","volume":"53","author":"Ong","year":"2011","journal-title":"Hepatology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/prot.22613","article-title":"Molecular mechanism of allosteric communication in the human PPAR\u03b1-RXR\u03b1 heterodimer","volume":"78","author":"Venalainen","year":"2010","journal-title":"Proteins Struct. Funct. Bioinf."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1039\/C8FO02375A","article-title":"Polysaccharides derived from natural sources regulate triglyceride and cholesterol metabolism: A review of the mechanisms","volume":"10","author":"Wu","year":"2019","journal-title":"Food Funct."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1161\/ATVBAHA.108.179689","article-title":"Fibrates, glitazones, and peroxisome proliferator-activated receptors","volume":"30","author":"Lalloyer","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.2337\/diabetes.50.9.2094","article-title":"PPAR\u03b3 ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein","volume":"50","author":"Maeda","year":"2001","journal-title":"Diabetes"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.3892\/mmr.2015.4639","article-title":"L-carnitine ameliorates the liver inflammatory response by regulating carnitine palmitoyltransferase i-dependent PPAR\u03b3 signaling","volume":"13","author":"Jiang","year":"2016","journal-title":"Mol. Med. Rep."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/14\/2232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:15:14Z","timestamp":1760109314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/14\/2232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":78,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["nu16142232"],"URL":"https:\/\/doi.org\/10.3390\/nu16142232","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,11]]}}}