{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:34:49Z","timestamp":1790087689340,"version":"4.0.1"},"reference-count":91,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["173520"],"award-info":[{"award-number":["173520"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["143325"],"award-info":[{"award-number":["143325"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CIHR Postdoctoral Fellowship","award":["173520"],"award-info":[{"award-number":["173520"]}]},{"name":"CIHR Postdoctoral Fellowship","award":["143325"],"award-info":[{"award-number":["143325"]}]},{"name":"The Research Institute of St. Joe\u2019s Hamilton","award":["173520"],"award-info":[{"award-number":["173520"]}]},{"name":"The Research Institute of St. Joe\u2019s Hamilton","award":["143325"],"award-info":[{"award-number":["143325"]}]},{"name":"Amgen Canada","award":["173520"],"award-info":[{"award-number":["173520"]}]},{"name":"Amgen Canada","award":["143325"],"award-info":[{"award-number":["143325"]}]},{"name":"Heart and Stroke Foundation of Ontario","award":["173520"],"award-info":[{"award-number":["173520"]}]},{"name":"Heart and Stroke Foundation of Ontario","award":["143325"],"award-info":[{"award-number":["143325"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objective: Metabolic Syndrome (MetS) affects hundreds of millions of individuals and constitutes a major cause of morbidity and mortality worldwide. Obesity is believed to be at the core of metabolic abnormalities associated with MetS, including dyslipidemia, insulin resistance, fatty liver disease and vascular dysfunction. Although previous studies demonstrate a diverse array of naturally occurring antioxidants that attenuate several manifestations of MetS, little is known about the (i) combined effect of these compounds on hepatic health and (ii) molecular mechanisms responsible for their effect. Methods: We explored the impact of a metabolic enhancer (ME), consisting of 7 naturally occurring antioxidants and mitochondrial enhancing agents, on diet-induced obesity, hepatic steatosis and atherogenic serum profile in mice. Results: Here we show that a diet-based ME supplementation and exercise have similar beneficial effects on adiposity and hepatic steatosis in mice. Mechanistically, ME reduced hepatic ER stress, fibrosis, apoptosis, and inflammation, thereby improving overall liver health. Furthermore, we demonstrated that ME improved HFD-induced pro-atherogenic serum profile in mice, similar to exercise. The protective effects of ME were reduced in proprotein convertase subtilisin\/kexin 9 (PCSK9) knock out mice, suggesting that ME exerts it protective effect partly in a PCSK9-dependent manner. Conclusions: Our findings suggest that components of the ME have a positive, protective effect on obesity, hepatic steatosis and cardiovascular risk and that they show similar effects as exercise training.<\/jats:p>","DOI":"10.3390\/nu15102410","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T03:57:32Z","timestamp":1684727852000},"page":"2410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Metabolic Enhancer Protects against Diet-Induced Obesity and Liver Steatosis and Corrects a Pro-Atherogenic Serum Profile in Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Khrystyna","family":"Platko","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Nephrology, McMaster University, and the Research Institute of St. Joe\u2019s Hamilton, Hamilton, ON L8N 4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Lebeau","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, McMaster University, and the Research Institute of St. Joe\u2019s Hamilton, Hamilton, ON L8N 4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Nederveen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Health Sciences, McMaster University Medical Centre (MUMC), Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, McMaster University, and the Research Institute of St. Joe\u2019s Hamilton, Hamilton, ON L8N 4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, McMaster University, and the Research Institute of St. Joe\u2019s Hamilton, Hamilton, ON L8N 4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University Medical Centre (MUMC), Hamilton, ON L8N 5Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0312-3746","authenticated-orcid":false,"given":"Mark","family":"Tarnopolsky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Health Sciences, McMaster University Medical Centre (MUMC), Hamilton, ON L8N 3Z5, Canada"},{"name":"Exerkine Corporation, MUMC, Hamilton, ON L8N 3Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-0865","authenticated-orcid":false,"given":"Richard","family":"Austin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, McMaster University, and the Research Institute of St. Joe\u2019s Hamilton, Hamilton, ON L8N 4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/ncb3169","article-title":"Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver","volume":"17","author":"Aiello","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.5223\/pghn.2020.23.3.189","article-title":"Novel Insights into the Pathogenesis and Management of the Metabolic Syndrome","volume":"23","author":"Wang","year":"2020","journal-title":"Pediatr. Gastroenterol. Hepatol. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-48382-5_1","article-title":"The Definition and Prevalence of Obesity and Metabolic Syndrome","volume":"960","author":"Engin","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17034","DOI":"10.1038\/nrdp.2017.34","article-title":"Obesity","volume":"3","author":"Hu","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15080","DOI":"10.1038\/nrdp.2015.80","article-title":"Nonalcoholic fatty liver disease","volume":"1","author":"Brunt","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jhep.2018.06.008","article-title":"Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease","volume":"69","author":"Lebeaupin","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1101\/gad.14.2.152","article-title":"An essential role in liver development for transcription factor XBP-1","volume":"14","author":"Reimold","year":"2000","journal-title":"Genes. Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1172\/JCI200521848","article-title":"The unfolded protein response sensor IRE1\u03b1 is required at 2 distinct steps in B cell lymphopoiesis","volume":"115","author":"Zhang","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cmet.2012.09.003","article-title":"IRE1\u03b1-XBP1s Induces PDI Expression to Increase MTP Activity for Hepatic VLDL Assembly and Lipid Homeostasis","volume":"16","author":"Wang","year":"2012","journal-title":"Cell Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16314","DOI":"10.1073\/pnas.0808517105","article-title":"PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation","volume":"105","author":"Hatzivassiliou","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/sj.emboj.7600106","article-title":"ATF6 modulates SREBP2-mediated lipogenesis","volume":"23","author":"Zeng","year":"2004","journal-title":"EMBO J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10497","DOI":"10.3390\/ijms140510497","article-title":"Obesity-Associated Oxidative Stress: Strategies Finalized to Improve Redox State","volume":"14","author":"Savini","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.3109\/10715762.2015.1078461","article-title":"Endoplasmic reticulum stress and Oxidative stress in the pathogenesis of Non-alcoholic fatty liver disease","volume":"49","author":"Ashraf","year":"2015","journal-title":"Free. Radic. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1001\/jama.2015.5370","article-title":"Nonalcoholic Fatty Liver Disease: A systematic review","volume":"313","author":"Rinella","year":"2015","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8591","DOI":"10.3390\/ijms15058591","article-title":"Evolving Concepts in the Pathogenesis of NASH: Beyond Steatosis and Inflammation","volume":"15","author":"Peverill","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.plipres.2012.10.004","article-title":"Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease","volume":"52","author":"Leamy","year":"2013","journal-title":"Prog. Lipid Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.jhep.2010.09.022","article-title":"Intracellular reactive oxygen species are required for directional migration of resident and bone marrow-derived hepatic pro-fibrogenic cells","volume":"54","author":"Novo","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yang, J., Fern\u00e1ndez-Galilea, M., Mart\u00ednez-Fern\u00e1ndez, L., Gonz\u00e1lez-Muniesa, P., P\u00e9rez-Ch\u00e1vez, A., Mart\u00ednez, J.A., and Moreno-Aliaga, M.J. (2019). Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation. Nutrients, 11.","DOI":"10.3390\/nu11040872"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s11789-017-0085-0","article-title":"PCSK9 targets important for lipid metabolism","volume":"12","author":"Schulz","year":"2017","journal-title":"Clin. Res. Cardiol. Suppl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1080\/07853890.2016.1188328","article-title":"Liver fat accumulation is associated with circulating PCSK9","volume":"48","author":"Ruscica","year":"2016","journal-title":"Ann. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.clinbiochem.2020.01.003","article-title":"Circulating PCSK9 is associated with liver biomarkers and hepatic steatosis","volume":"77","author":"Paquette","year":"2020","journal-title":"Clin. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"158792","DOI":"10.1016\/j.bbalip.2020.158792","article-title":"Hepatic and circulating levels of PCSK9 in morbidly obese patients: Relation with severity of liver steatosis","volume":"1865","author":"Emma","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9037","DOI":"10.1074\/jbc.RA119.008094","article-title":"Diet-induced hepatic steatosis abrogates cell-surface LDLR by inducing de novo PCSK9 expression in mice","volume":"294","author":"Lebeau","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.jhepr.2019.10.009","article-title":"Pcsk9 knockout exacerbates diet-induced non-alcoholic steatohepatitis, fibrosis and liver injury in mice","volume":"1","author":"Lebeau","year":"2019","journal-title":"JHEP Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1074\/jbc.M116.744235","article-title":"Endoplasmic Reticulum Stress and Ca2+ Depletion Differentially Modulate the Sterol Regulatory Protein PCSK9 to Control Lipid Metabolism","volume":"292","author":"Lebeau","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7329","DOI":"10.1074\/jbc.RA117.001049","article-title":"Loss-of-function PCSK9 mutants evade the unfolded protein response sensor GRP78 and fail to induce endoplasmic reticulum stress when retained","volume":"293","author":"Lebeau","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e128650","DOI":"10.1172\/JCI128650","article-title":"The loss-of-function PCSK9Q152H variant increases ER chaperones GRP78 and GRP94 and protects against liver injury","volume":"131","author":"Lebeau","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41575-020-00408-y","article-title":"Therapeutic pipeline in nonalcoholic steatohepatitis","volume":"18","author":"Vuppalanchi","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.2147\/PPA.S103649","article-title":"Weight-loss intervention adherence and factors promoting adherence: A meta-analysis","volume":"10","author":"Lemstra","year":"2016","journal-title":"Patient Prefer. Adherence"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3727\/105221617X15124844266408","article-title":"The Effects of Physical Exercise on Fatty Liver Disease","volume":"18","author":"Sud","year":"2018","journal-title":"Gene Expr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1038\/oby.2009.126","article-title":"Diet and Exercise Interventions Reduce Intrahepatic Fat Content and Improve Insulin Sensitivity in Obese Older Adults","volume":"17","author":"Shah","year":"2009","journal-title":"Obesity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1002\/hep.27544","article-title":"Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: A retrospective study","volume":"61","author":"Oh","year":"2015","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.bbrc.2011.08.097","article-title":"Regular exercise prevents high-sucrose diet-induced fatty liver via improvement of hepatic lipid metabolism","volume":"413","author":"Aoi","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.mito.2014.03.012","article-title":"Physical exercise prevents and mitigates non-alcoholic steatohepatitis-induced liver mitochondrial structural and bioenergetics impairments","volume":"15","author":"Passos","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1177\/1753944717711379","article-title":"Metabolic syndrome: Pathophysiology, management, and modulation by natural compounds","volume":"11","author":"Rochlani","year":"2017","journal-title":"Ther. Adv. Cardiovasc. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Silva Figueiredo, P., Inada, A.C., Ribeiro Fernandes, M., Granja Arakaki, D., Freitas, K.C., Avellaneda Guimaraes, R.C., Aragao do Nascimento, V., and Aiko Hiane, P. (2018). An Overview of Novel Dietary Supplements and Food Ingredients in Patients with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease. Molecules, 23.","DOI":"10.3390\/molecules23040877"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5374","DOI":"10.1073\/pnas.0501652102","article-title":"Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9","volume":"102","author":"Rashid","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1142\/S0192415X18500325","article-title":"Epigallocatechin-3-Gallate-Rich Green Tea Extract Ameliorates Fatty Liver and Weight Gain in Mice Fed a High Fat Diet by Activating the Sirtuin 1 and AMP Activating Protein Kinase Pathway","volume":"46","author":"Bae","year":"2018","journal-title":"Am. J. Chin. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1093\/jn\/138.9.1677","article-title":"The Major Green Tea Polyphenol, (-)-Epigallocatechin-3-Gallate, Inhibits Obesity, Metabolic Syndrome, and Fatty Liver Disease in High-Fat\u2013Fed Mice","volume":"138","author":"Bose","year":"2008","journal-title":"J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1016\/j.dsx.2019.03.021","article-title":"The effects of green tea on lipid metabolism and its potential applications for obesity and related metabolic disorders-An existing update","volume":"13","author":"Dinh","year":"2019","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"108324","DOI":"10.1016\/j.jnutbio.2019.108324","article-title":"Green tea polyphenols decrease weight gain, ameliorate alteration of gut microbiota, and mitigate intestinal inflammation in canines with high-fat-diet-induced obesity","volume":"78","author":"Li","year":"2020","journal-title":"J. Nutr. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.apjtm.2016.05.017","article-title":"Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice","volume":"9","author":"Choi","year":"2016","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"H.V., S., K, V., Patel, D., and K, S. (2016). Biomechanism of chlorogenic acid complex mediated plasma free fatty acid metabolism in rat liver. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1258-y"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1080\/10826068.2020.1786699","article-title":"The chemistry of chlorogenic acid from green coffee and its role in attenuation of obesity and diabetes","volume":"50","author":"Pimpley","year":"2020","journal-title":"Prep. Biochem. Biotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"718379","DOI":"10.1155\/2014\/718379","article-title":"Decaffeinated Green Coffee Bean Extract Attenuates Diet-Induced Obesity and Insulin Resistance in Mice","volume":"2014","author":"Song","year":"2014","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1517\/13543784.13.12.1641","article-title":"Alpha-lipoic acid, an anti-obesity agent?","volume":"13","author":"Doggrell","year":"2004","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"El Midaoui, A., Fantus, I.G., Boughrous, A.A., and Couture, R. (2019). Beneficial Effects of Alpha-Lipoic Acid on Hypertension, Visceral Obesity, UCP-1 Expression and Oxidative Stress in Zucker Diabetic Fatty Rats. Antioxidants, 8.","DOI":"10.3390\/antiox8120648"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1007\/s12072-012-9387-y","article-title":"Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: Double-blind, randomized clinical trial of efficacy and safety","volume":"7","author":"Gianturco","year":"2012","journal-title":"Hepatol. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.clnu.2017.06.002","article-title":"Alpha-lipoic acid supplement in obesity treatment: A systematic review and meta-analysis of clinical trials","volume":"37","author":"Namazi","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3109\/10520295.2014.883463","article-title":"The effects of forskolin and rolipram on cAMP, cGMP and free fatty acid levels in diet induced obesity","volume":"89","author":"Doseyici","year":"2013","journal-title":"Biotech. Histochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.1111\/bph.13611","article-title":"Forskolin, a hedgehog signalling inhibitor, attenuates carbon tetrachloride-induced liver fibrosis in rats","volume":"173","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0022-2275(20)41542-1","article-title":"Relationship between cyclic AMP production and lipolysis induced by forskolin in rat fat cells","volume":"33","author":"Okuda","year":"1992","journal-title":"J. Lipid Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1039\/C8FO01236A","article-title":"Coenzyme Q10 attenuates high-fat diet-induced non-alcoholic fatty liver disease through activation of the AMPK pathway","volume":"10","author":"Chen","year":"2019","journal-title":"Food Funct."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4149\/BLL_2012_005","article-title":"Ratio of lipid parameters to coenzyme Q10 could be used as biomarker of the development of early complications of obesity in children","volume":"113","author":"Gvozdjakova","year":"2012","journal-title":"Bratisl. Med. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.arcmed.2019.04.004","article-title":"Independent and Additive Effects of Coenzyme Q10 and Vitamin E on Cardiometabolic Outcomes and Visceral Adiposity in Women With Polycystic Ovary Syndrome","volume":"50","author":"Izadi","year":"2019","journal-title":"Arch. Med. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/j.bcp.2009.07.008","article-title":"Coenzyme Q10 supplementation lowers hepatic oxidative stress and inflammation associated with diet-induced obesity in mice","volume":"78","author":"Sohet","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1002\/ptr.6653","article-title":"Biological effects of red beetroot and betalains: A review","volume":"34","author":"Hadipour","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/1476-511X-10-178","article-title":"Physiological properties of beetroot crisps applied in standard and dyslipidaemic diets of rats","volume":"10","author":"Wroblewska","year":"2011","journal-title":"Lipids Health Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1681\/ASN.2008040349","article-title":"Association of Serum Phosphate with Vascular and Valvular Calcification in Moderate CKD","volume":"20","author":"Adeney","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Napolitano, G., Fasciolo, G., Di Meo, S., and Venditti, P. (2019). Vitamin E Supplementation and Mitochondria in Experimental and Functional Hyperthyroidism: A Mini-Review. Nutrients, 11.","DOI":"10.3390\/nu11122900"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/S0891-5849(97)00136-6","article-title":"Effect of Vitamin E and Probucol on Dietary Cholesterol-Induced Atherosclerosis in Rabbits","volume":"24","author":"Taha","year":"1998","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbadis.2018.10.010","article-title":"Vitamin E alleviates non-alcoholic fatty liver disease in phosphatidylethanolamine N-methyltransferase deficient mice","volume":"1865","author":"Presa","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1161\/01.CIR.102.1.82","article-title":"Vitamin E Reduces the Uptake of Oxidized LDL by Inhibiting CD36 Scavenger Receptor Expression in Cultured Aortic Smooth Muscle Cells","volume":"102","author":"Ricciarelli","year":"2000","journal-title":"Circulation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.molmet.2019.06.021","article-title":"GDF10 blocks hepatic PPAR\u03b3 activation to protect against diet-induced liver injury","volume":"27","author":"Platko","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1161\/ATVBAHA.119.313779","article-title":"TDAG51 (T-Cell Death-Associated Gene 51) Is a Key Modulator of Vascular Calcification and Osteogenic Transdifferentiation of Arterial Smooth Muscle Cells","volume":"40","author":"Platko","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Nederveen, J.P., Manta, K., Bujak, A.L., Simone, A.C., Fuda, M.R., Nilsson, M.I., Hettinga, B.P., Hughes, M.C., Perry, C.G., and Tarnopolsky, M.A. (2021). A Novel Multi-Ingredient Sup-plement Activates a Browning Program in White Adipose Tissue and Mitigates Weight Gain in High-Fat Diet-Fed Mice. Nutrients, 13.","DOI":"10.3390\/nu13113726"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1038\/s41467-019-09753-2","article-title":"Caspase-1 initiates apoptosis in the absence of gasdermin D","volume":"10","author":"Tsuchiya","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1016\/j.jhep.2014.12.012","article-title":"NAFLD: A multisystem disease","volume":"62","author":"Byrne","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Tana, C., Ballestri, S., Ricci, F., Di Vincenzo, A., Ticinesi, A., Gallina, S., Giamberardino, M.A., Cipollone, F., Sutton, R., and Vettor, R. (2019). Cardiovascular Risk in Non-Alcoholic Fatty Liver Disease: Mechanisms and Therapeutic Implications. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16173104"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Myers, J., Kokkinos, P., and Nyelin, E. (2019). Physical Activity, Cardiorespiratory Fitness, and the Metabolic Syndrome. Nutrients, 11.","DOI":"10.3390\/nu11071652"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3389\/fpubh.2019.00135","article-title":"Proportion of Adults Meeting the 2018 Physical Activity Guidelines for Americans According to Accelerometers","volume":"7","author":"Zenko","year":"2019","journal-title":"Front. Public Health"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1684\/ecn.2018.0415","article-title":"Obesity and inflammation","volume":"29","author":"Karczewski","year":"2018","journal-title":"Eur. Cytokine Netw."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Santamarina, A.B., Oliveira, J.L., Silva, F.P., Carnier, J., Mennitti, L.V., Santana, A.A., De Souza, G.H.I., Ribeiro, E.B., Oller do Nascimento, C.M., and Lira, F.S. (2015). Green Tea Extract Rich in Epigallocatechin-3-Gallate Prevents Fatty Liver by AMPK Activation via LKB1 in Mice Fed a High-Fat Diet. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141227"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Vel\u00e1zquez, A.M., Roglans, N., Bentanachs, R., Gen\u00e9, M., Sala-Vila, A., L\u00e1zaro, I., Rodr\u00edguez-Morat\u00f3, J., S\u00e1nchez, R.M., Laguna, J.C., and Alegret, M. (2020). Effects of a Low Dose of Caffeine Alone or as Part of a Green Coffee Extract, in a Rat Dietary Model of Lean Non-Alcoholic Fatty Liver Disease without Inflammation. Nutrients, 12.","DOI":"10.3390\/nu12113240"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.jnutbio.2014.06.001","article-title":"Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1\/LKB1\/AMPK pathway","volume":"25","author":"Yang","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3389\/fphar.2017.00444","article-title":"Vitamin E As a Potential Interventional Treatment for Metabolic Syndrome: Evidence from Animal and Human Studies","volume":"8","author":"Wong","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_78","first-page":"47","article-title":"Coleus forskohlii","volume":"11","author":"Research","year":"2006","journal-title":"Altern. Med. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1445-5994.2006.01295.x","article-title":"Effects of vitamin E treatment on peroxisome proliferator-activated receptor-? expression and insulin resistance in patients with non-alcoholic steatohepatitis: Results of a pilot study","volume":"37","author":"Yakaryilmaz","year":"2007","journal-title":"Intern. Med. J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1056\/NEJMoa0907929","article-title":"Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis","volume":"362","author":"Sanyal","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/j.1439-0396.2007.00752.x","article-title":"Liver lipid metabolism","volume":"92","author":"Nguyen","year":"2008","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.dld.2016.03.016","article-title":"The essential functions of endoplasmic reticulum chaperones in hepatic lipid metabolism","volume":"48","author":"Zhang","year":"2016","journal-title":"Dig. Liver Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1463-1326.2010.01275.x","article-title":"Hepatic steatosis: A role for de novo lipogenesis and the transcription factor SREBP-1c","volume":"12","author":"Foufelle","year":"2010","journal-title":"Diabetes Obes. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1016\/j.jnutbio.2015.07.002","article-title":"Decaffeinated green tea extract rich in epigallocatechin-3-gallate prevents fatty liver disease by increased activities of mitochondrial respiratory chain complexes in diet-induced obesity mice","volume":"26","author":"Santamarina","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1248\/yakushi.125.449","article-title":"Effects of Coleus forskohlii on Fat Storage in Ovariectomized Rats","volume":"125","author":"Han","year":"2005","journal-title":"Yakugaku Zasshi"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/iub.2020","article-title":"Vitamin E: Regulatory role in the cardiovascular system","volume":"71","author":"Sozen","year":"2019","journal-title":"IUBMB Life"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/ptr.5583","article-title":"A Review of Natural Stimulant and Non-stimulant Thermogenic Agents","volume":"30","author":"Stohs","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s12967-020-02362-4","article-title":"Beneficial impact of epigallocatechingallate on LDL-C through PCSK9\/LDLR pathway by blocking HNF1\u03b1 and activating FoxO3a","volume":"18","author":"Cui","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1600836","DOI":"10.1002\/mnfr.201600836","article-title":"Epigallocatechin gallate induces an up-regulation of LDL receptor accompanied by a reduction of PCSK9 via the annexin A2-independent pathway in HepG2 cells","volume":"61","author":"Kitamura","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"9820","DOI":"10.1073\/pnas.0903849106","article-title":"A proprotein convertase subtilisin\/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates","volume":"106","author":"Chan","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"8665","DOI":"10.1073\/pnas.0903485106","article-title":"Antioxidants prevent health-promoting effects of physical exercise in humans","volume":"106","author":"Ristow","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/10\/2410\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:39:41Z","timestamp":1760125181000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/10\/2410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,22]]},"references-count":91,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["nu15102410"],"URL":"https:\/\/doi.org\/10.3390\/nu15102410","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,22]]}}}