Therapeutic Efficacy of Antioxidants in Ameliorating Obesity Phenotype and Associated Comorbidities

Steven Tun1, Caleb James Spainhower1, Cameron L. Cottrill1, Hari Vishal Lakhani1, Sneha S. Pillai1, Anum Dilip1, Hibba Chaudhry1, Joseph I. Shapiro1, Komal Sodhi1
1Departments of Medicine, Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, United States

Tóm tắt

Từ khóa


Tài liệu tham khảo

Achari, 2017, Adiponectin, a Therapeutic Target for Obesity,Diabetes, and Endothelial Dysfunction, Int. J. Mol. Sci., 18, 10.3390/ijms18061321

Achkasov, 2016, Pathogenetically targeted method for conservative treatment of obesity and overweight correction, Klin. Med. (Mosk), 94, 509, 10.18821/0023-2149-2016-94-7-509-517

Aggarwal, 2006, Inflammation and cancer: how hot is thelink, Biochem. Pharmacol., 72, 1605, 10.1016/j.bcp.2006.06.029

Aggarwal, 2010, Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals, Annu. Rev. Nutr., 30, 173, 10.1146/annurev.nutr.012809.104755

Ahmad, 2018, Role of Nitric Oxide in the Cardiovascular and Renal Systems, Int. J. Mol. Sci., 19, 10.3390/ijms19092605

Ahsan, 2015, A review of characterization of tocotrienols from plant oils and foods, J. Chem. Biol., 8, 45, 10.1007/s12154-014-0127-8

Alcala, 2015, Vitamin E reduces adipose tissue fibrosis, inflammation, and oxidative stress and improves metabolic profile in obesity, Obes. (Silver Spring), 23, 1598, 10.1002/oby.21135

Allen, 2011, Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers, J. Altern. Complement Med., 17, 827, 10.1089/acm.2010.0716

Ammon, 1992, Increase in glucose consumption by acetylcysteine during hyperglycemic clamp. A study with healthy volunteers, Arzneimittelforschung, 42, 642

Anderson, 2010, Hypercoagulable states, Clin. Chest Med., 31, 659, 10.1016/j.ccm.2010.07.004

Anhe, 2015, A polyphenol-rich cranberry extract protectsfrom diet-induced obesity, insulin resistance and intestinal inflammation in association withincreased Akkermansia spp. population in the gut microbiota of mice, Gut, 64, 872, 10.1136/gutjnl-2014-307142

Aprahamian, 2011, Adiponectin in cardiovascular inflammation and obesity, Int. J. Inflam., 2011, 376909, 10.4061/2011/376909

Araujo, 2012, Heme oxygenase-1, oxidation, inflammation, and atherosclerosis, Front. Pharmacol., 3, 10.3389/fphar.2012.00119

Asai, 2004, Biotransformation of fucoxanthinol into amarouciaxanthin A in mice and HepG2 cells: formation and cytotoxicity of fucoxanthin metabolites, Drug Metab. Dispos., 32, 205, 10.1124/dmd.32.2.205

Assari, 2019, Baseline Obesity Increases 25-Year Risk of Mortality due to Cerebrovascular Disease: Role of Race, Int. J. Environ. Res. Public Health, 16, 10.3390/ijerph16193705

Ayer, 2016, Heme Oxygenases in Cardiovascular Health and Disease, Physiol. Rev., 96, 1449, 10.1152/physrev.00003.2016

Babu, 1997, Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats, Mol. Cell Biochem., 166, 169, 10.1023/A:1006819605211

Balla, 1992, Ferritin: a cytoprotective antioxidant strategem of endothelium, J. Biol. Chem., 267, 18148, 10.1016/S0021-9258(19)37165-0

Baxter, 2012, Plasma and tissue concentrations of alpha-tocopherol and delta-tocopherol following high dose dietary supplementation in mice, Nutrients, 4, 467, 10.3390/nu4060467

Beck, 2010, Interplay between heme oxygenase-1 and the multifunctional transcription factor yin yang 1 in the inhibition of intimal hyperplasia, Circ. Res., 107, 1490, 10.1161/CIRCRESAHA.110.231985

Beppu, 2012, Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-A(y) mice, Lipids Health Dis., 11, 112, 10.1186/1476-511X-11-112

Beppu, 2013, Down-regulation of hepatic stearoyl-CoA desaturase-1 expression by fucoxanthin via leptin signaling in diabetic/obese KK-A(y) mice, Lipids, 48, 449, 10.1007/s11745-013-3784-4

Bereczki, 2018, Heme Oxygenase-1: Clinical Relevance in Ischemic Stroke, Curr. Pharm. Des., 24, 2229, 10.2174/1381612824666180717101104

Berrington de Gonzalez, 2010, Body-mass index and mortality among 1.46million white adults, N. Engl. J. Med., 363, 2211, 10.1056/NEJMoa1000367

Berry, 2012, Retinoic acid upregulates preadipocyte genes to block adipogenesis and suppress diet-induced obesity, Diabetes, 61, 1112, 10.2337/db11-1620

Beydoun, 2019, Carotenoids, vitamin A, and their association with the metabolic syndrome: a systematic review and meta-analysis, Nutr. Rev., 77, 32, 10.1093/nutrit/nuy044

Bhatti, 2017, Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies, Biochim. Biophys. Acta Mol. Basis Dis., 1863, 1066, 10.1016/j.bbadis.2016.11.010

Blokhin, 2013, Mechanisms of thrombosis in obesity, Curr. Opin. Hematol., 20, 437, 10.1097/MOH.0b013e3283634443

Bohn, 2017, Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans, Mol. Nutr. Food Res., 61, 10.1002/mnfr.201600685

Boscoboinik, 1991, Inhibition of cell proliferation by alpha-tocopherol. Role of protein kinase C, J. Biol. Chem., 266, 6188, 10.1016/S0021-9258(18)38102-X

Burgess, 2010, Adipocyte heme oxygenase-1 induction attenuates metabolic syndrome in both male and female obese mice, Hypertension, 56, 1124, 10.1161/HYPERTENSIONAHA.110.151423

Burhans, 2018, Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus, Compr. Physiol., 9, 1, 10.1002/cphy.c170040

Calzadilla, 2011, N-acetylcysteine reduces markers of differentiation in 3T3-L1 adipocytes, Int. J. Mol. Sci., 12, 6936, 10.3390/ijms12106936

Canas, 2017, Effects of Mixed Carotenoids on Adipokines and Abdominal Adiposity in Children: A Pilot Study, J. Clin. Endocrinol. Metab., 102, 1983, 10.1210/jc.2017-00185

Cao, 2012, Heme oxygenase gene targeting to adipocytes attenuates adiposity and vascular dysfunction in mice fed a high-fat diet, Hypertension, 60, 467, 10.1161/HYPERTENSIONAHA.112.193805

Carlsen, 2009, Diet-induced obesity increases NF-kappaB signaling in reporter mice, Genes Nutr., 4, 215, 10.1007/s12263-009-0133-6

Castro-Barquero, 2018, Relationship between Mediterranean Dietary Polyphenol Intake and Obesity, Nutrients, 10, 10.3390/nu10101523

Chait, 2020, Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease, Front. Cardiovasc. Med., 7, 10.3389/fcvm.2020.00022

Chan, 2011, Haem oxygenase-1 and cardiovascular disease: mechanisms and therapeutic potential, Clin. Sci. (Lond), 120, 493, 10.1042/CS20100508

Chen, 1985, N-acetylcysteine reverses cardiac myocytedysfunction in a rodent model of behavioral stress, J. Appl. Physiol., 514, 10.1152/japplphysiol.01471.2012

Cheng, 2009, Heme oxygenase 1 determines atherosclerotic lesion progression into a vulnerable plaque, Circulation, 119, 3017, 10.1161/CIRCULATIONAHA.108.808618

Chouchani, 2017, Mitochondrial reactive oxygen species and adipose tissue thermogenesis: Bridging physiology and mechanisms, J. Biol. Chem., 292, 16810, 10.1074/jbc.R117.789628

Colombo, 2010, tocopherol and tocotrienol-perspectives, Molecules, 15, 2103, 10.3390/molecules15042103

Cook-Mills, 2013, Two faces of vitamin E in the lung, Am. J. Respir. Crit. Care Med., 188, 279, 10.1164/rccm.201303-0503ED

Cook-Mills, 2013, Isoforms of Vitamin E Differentially Regulate PKC alpha and Inflammation: A Review, J. Clin. Cell Immunol., 4, 10.4172/2155-9899.1000137

Coronel, 2019, beta-carotene in Obesity Research: Technical Considerations and Current Status of the Field, Nutrients, 11, 10.3390/nu11040842

Craver, 2020, N-acetylcysteine inhibits thrombosis in a murine model of myeloproliferative neoplasm, Blood Adv., 4, 312, 10.1182/bloodadvances.2019000967

Cui, 2014, Overexpression of superoxide dismutase 3 gene blocks high-fat diet-induced obesity, fatty liver and insulin resistance, Gene Ther., 21, 840, 10.1038/gt.2014.64

de Almeida, 2020, Unveiling the Role of Inflammation and Oxidative Stress on Age-Related Cardiovascular Diseases, Oxid. Med. Cell Longev., 2020, 1954398, 10.1155/2020/1954398

de Andrade, 2015, Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine, Int. J. Mol. Sci., 16, 30269, 10.3390/ijms161226225

de Mello, 2018, Mitochondrial dysfunction in obesity, Life Sci., 192, 26, 10.1016/j.lfs.2017.11.019

Dela Cruz, 2018, Mitochondrial dysfunction and damage associated molecular patterns (DAMPs) in chronic inflammatory diseases, Mitochondrion, 41, 37, 10.1016/j.mito.2017.12.001

Diniz, 2006, Effects of N-acetylcysteine on sucrose-rich diet-induced hyperglycaemia, dyslipidemia and oxidative stress in rats, Eur. J. Pharmacol., 543, 151, 10.1016/j.ejphar.2006.05.039

Dludla, 2017, Cardioprotective potential of N-acetyl cysteine against hyperglycaemia-induced oxidative damage: a protocol for a systematic review, Syst. Rev., 6, 96, 10.1186/s13643-017-0493-8

Donohoe, 2020, Mitogen-Activated Protein Kinase (MAPK) and Obesity-Related Cancer, Int. J. Mol. Sci., 21, 10.3390/ijms21041241

Durante, 2003, Heme oxygenase-1 in growth control and its clinical application to vascular disease, J. Cell Physiol., 195, 373, 10.1002/jcp.10274

Durante, 2011, Protective role of heme oxygenase-1 against inflammation in atherosclerosis, Front. Biosci. (Landmark Ed), 16, 2372, 10.2741/3860

Dutra, 2014, Heme on innate immunity and inflammation, Front. Pharmacol., 5, 10.3389/fphar.2014.00115

Dutton, 2008, Regulation of angiopoietin-like protein 4/fasting-induced adipose factor (Angptl4/FIAF) expression in mouse white adipose tissue and 3T3-L1 adipocytes, Br. J. Nutr., 100, 18, 10.1017/S0007114507882961

Eder, 2004, Effects of a dietary oxidized fat on cholesterol in plasma and lipoproteins and the susceptibility of low-density lipoproteins to lipid peroxidation in guinea pigs fed diets with different concentrations of vitamins E and C, Int. J. Vitam Nutr. Res., 74, 11, 10.1024/0300-9831.74.1.11

Engin, 2009, Alpha-tocopherol: looking beyond an antioxidant, Mol. Vis., 15, 855

Fisher, 2018, The phospholipase A2 activity of peroxiredoxin 6, J. Lipid Res., 59, 1132, 10.1194/jlr.R082578

Fonseca-Alaniz, 2007, Adipose tissue as an endocrine organ: from theory to practice, J. Pediatr. (Rio J), 83, S192, 10.2223/JPED.1709

Fraga, 2019, The effects of polyphenols and other bioactives on human health, Food Funct., 10, 514, 10.1039/C8FO01997E

Friedman, 1998, Leptin and the regulation of body weight inmammals, Nature, 395, 763, 10.1038/27376

Frismantiene, 2018, Smooth muscle cell-driven vascular diseases and molecular mechanisms of VSMC plasticity, Cell Signal, 52, 48, 10.1016/j.cellsig.2018.08.019

Fruh, 2017, Obesity: Risk factors, complications, and strategies for sustainable long-term weight management, J. Am. Assoc. Nurse Pract., 29, S3, 10.1002/2327-6924.12510

Fukai, 2011, Superoxide dismutases: role in redox signaling, vascular function, and diseases, Antioxid. Redox Signal, 15, 1583, 10.1089/ars.2011.3999

Fulghesu, 2002, N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome, Fertil. Steril., 77, 1128, 10.1016/S0015-0282(02)03133-3

Furchgott, 1991, Endothelium-dependent and -independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide, carbon monoxide and light, Blood Vessels, 28, 52, 10.1159/000158843

Galiniak, 2019, Health benefits of resveratrol administration, Acta Biochim. Pol., 66, 13, 10.18388/abp.2018_2749

Galmes, 2018, Vitamin E Metabolic Effects and Genetic Variants: A Challenge for Precision Nutrition in Obesity and Associated Disturbances, Nutrients, 10, 10.3390/nu10121919

Gibson, 2011, Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes, Cardiovasc. Diabetol., 10, 43, 10.1186/1475-2840-10-43

Girouard, 2003, N-acetylcysteine improves nitric oxide and alpha-adrenergic pathways in mesenteric beds of spontaneously hypertensive rats, Am. J. Hypertens., 16, 577, 10.1016/S0895-7061(03)00863-X

Gozzelino, 2010, Mechanisms of cell protection by heme oxygenase-1, Annu. Rev. Pharmacol. Toxicol., 50, 323, 10.1146/annurev.pharmtox.010909.105600

Grigsby, 2001, Inhibition of ceramide production reverses TNF-induced insulin resistance, Biochem. Biophys. Res. Commun., 287, 1121, 10.1006/bbrc.2001.5694

Haczeyni, 2018, Causes and mechanisms of adipocyte enlargement and adipose expansion, Obes. Rev., 19, 406, 10.1111/obr.12646

Haleagrahara, 2011, N-acetylcysteine offers cardioprotection by decreasing cardiac lipid hydroperoxides and 8-isoprostane level in isoproterenol-induced cardiotoxicity in rats, Cardiovasc. Toxicol., 11, 373, 10.1007/s12012-011-9132-0

Hall, 2009, Typical 2-Cys peroxiredoxins–structures, mechanisms and functions, FEBS J., 276, 2469, 10.1111/j.1742-4658.2009.06985.x

Hammarstedt, 2018, Impaired Adipogenesis and Dysfunctional Adipose Tissue in Human Hypertrophic Obesity, Physiol. Rev., 98, 1911, 10.1152/physrev.00034.2017

Hashimoto, 2009, The distribution and accumulation of fucoxanthin and its metabolites after oral administration in mice, Br. J. Nutr., 102, 242, 10.1017/S0007114508199007

Heeba, 2009, Anti-atherogenic effect of statins: role of nitric oxide, peroxynitrite and haem oxygenase-1, Br. J. Pharmacol., 156, 1256, 10.1111/j.1476-5381.2009.00125.x

Hennig, 2006, Linoleic acid induces proinflammatory events in vascular endothelial cells via activation of PI3K/Akt and ERK1/2 signaling, J. Nutr. Biochem., 17, 766, 10.1016/j.jnutbio.2006.01.005

Hernandez-Corbacho, 2015, Tumor Necrosis Factor-alpha (TNFalpha)-induced Ceramide Generation via Ceramide Synthases Regulates Loss of Focal Adhesion Kinase (FAK) and Programmed Cell Death, J. Biol. Chem., 290, 25356, 10.1074/jbc.M115.658658

Hosick, 2012, Heme oxygenase, a novel target for the treatmentof hypertension and obesity, Am. J. Physiol. Regul. Integr. Comp. Physiol., 302, R207, 10.1152/ajpregu.00517.2011

Houtkooper, 2012, Sirtuins as regulators of metabolism and healthspan, Nat. Rev. Mol. Cell Biol., 13, 225, 10.1038/nrm3293

Hruby, 2015, The Epidemiology of Obesity: A Big Picture, Pharmacoeconomics, 33, 673, 10.1007/s40273-014-0243-x

Hu, 2012, Combination of fucoxanthin and conjugated linoleic acid attenuates body weight gain and improves lipid metabolism in high-fat diet-induced obese rats, Arch. Biochem. Biophys., 519, 59, 10.1016/j.abb.2012.01.011

Huang, 2014, The anti-obesity effects of green tea in human intervention and basic molecular studies, Eur. J. Clin. Nutr., 68, 1075, 10.1038/ejcn.2014.143

Huang, 2018, Serum Beta Carotene and Overall and Cause-Specific Mortality, Circ. Res., 123, 1339, 10.1161/CIRCRESAHA.118.313409

Huh, 2012, Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression, Antioxid. Redox Signal, 16, 229, 10.1089/ars.2010.3766

Hwang, 2013, Inhibitory cross-talk between the AMPK and ERK pathways mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle, Br. J. Pharmacol., 169, 69, 10.1111/bph.12124

Ighodaro, 2018, Molecular pathways associated with oxidative stress in diabetes mellitus, BioMed. Pharmacother., 108, 656, 10.1016/j.biopha.2018.09.058

Jaoude, 2016, Matrix metalloproteinases in exercise and obesity, Vasc. Health Risk Manag., 12, 287, 10.2147/VHRM.S103877

Johnson, 2018, Effects of carotenoids on lipid bilayers, Phys. Chem. Chem. Phys., 20, 3795, 10.1039/C7CP07126D

Kachur, 2017, Obesity and cardiovasculardiseases, Minerva Med., 108, 212, 10.23736/S0026-4806.17.05022-4

Kang, 2011, Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes, Biochem. Biophys. Res. Commun., 409, 769, 10.1016/j.bbrc.2011.05.086

Kawanaka, 2013, Treatment of nonalcoholic steatohepatitis with vitamins E and C: a pilot study, Hepat. Med., 5, 11, 10.2147/HMER.S41258

Kerksick, 2005, The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stress, J. Int. Soc. Sports Nutr., 2, 38, 10.1186/1550-2783-2-2-38

Khan, 2018, Tea Polyphenols in Promotion of Human Health, Nutrients, 11, 10.3390/nu11010039

Khitan, 2014, HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets, J. Nutr. Metab., 2014, 980547, 10.1155/2014/980547

Kim, 2007, Obesity-associated improvements in metabolic profile through expansion of adipose tissue, J. Clin. Invest., 117, 2621, 10.1172/JCI31021

Kim, 2008, Heme oxygenase-mediated increases in adiponectin decrease fat content and inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 in Zucker rats and reduce adipogenesis in human mesenchymal stem cells, J. Pharmacol. Exp. Ther., 325, 833, 10.1124/jpet.107.135285

Kim, 2018, Peroxiredoxin 5 regulates adipogenesis-attenuating oxidative stress in obese mouse models induced by a high-fat diet, Free Radic. Biol. Med., 123, 27, 10.1016/j.freeradbiomed.2018.05.061

Kim, 2020, Peroxiredoxin 5 ameliorates obesity-induced non-alcoholic fatty liver disease through the regulation of oxidative stress and AMP-activated protein kinase signaling, Redox Biol., 28, 101315, 10.1016/j.redox.2019.101315

Kirmizis, 2009, Antiatherogenic effects of vitamin E: the search for the Holy Grail, Vasc. Health Risk Manag., 5, 767, 10.2147/VHRM.S5532

Korou, 2010, Comparative antilipidemic effect of N-acetylcysteine and sesame oil administration in diet-induced hypercholesterolemic mice, Lipids Health Dis., 9, 23, 10.1186/1476-511X-9-23

Korou, 2014, Impact of N-acetylcysteine and sesame oil on lipid metabolism and hypothalamic-pituitary-adrenal axis homeostasis in middle-aged hypercholesterolemic mice, Sci. Rep., 4, 6806, 10.1038/srep06806

Kruger, 2006, Up-regulation of heme oxygenase provides vascular protection in an animal model of diabetes through its antioxidant and antiapoptotic effects, J. Pharmacol. Exp. Ther., 319, 1144, 10.1124/jpet.106.107482

Kuk, 2011, Edmonton Obesity Staging System: association with weight history and mortality risk, Appl. Physiol. Nutr. Metab., 36, 570, 10.1139/h11-058

Kumar, 2005, Free heme toxicity and its detoxification systems in human, Toxicol. Lett., 157, 175, 10.1016/j.toxlet.2005.03.004

Kuroda, 2017, Adipocyte Death and Chronic Inflammation in Obesity, J. Med. Invest., 64, 193, 10.2152/jmi.64.193

Kuroda, 2010, NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart, Proc. Natl. Acad. Sci. U.S.A., 107, 15565, 10.1073/pnas.1002178107

Kuznetsov, 1993, [The use of antioxidants (alpha-tocopherol acetate) in the treatment of diabetes mellitus], Probl. Endokrinol. (Mosk), 39, 9, 10.14341/probl11942

Lagouge, 2006, Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha, Cell, 127, 1109, 10.1016/j.cell.2006.11.013

Lakhani, 2018, Phenotypic Alteration of Hepatocytes in Non-Alcoholic Fatty Liver Disease, Int. J. Med. Sci., 15, 1591, 10.7150/ijms.27953

Langi, 2018, Carotenoids: From Plants to Food and Feed Industries, Methods Mol. Biol., 1852, 57, 10.1007/978-1-4939-8742-9_3

Lasram, 2015, A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development, Clin. Biochem., 48, 1200, 10.1016/j.clinbiochem.2015.04.017

Lauby-Secretan, 2019, [Obesity and Cancer], Bull. Cancer, 106, 635, 10.1016/j.bulcan.2019.04.008

Lauhio, 2016, Association of MMP-8 with obesity, smoking and insulin resistance, Eur. J. Clin. Invest., 46, 757, 10.1111/eci.12649

Lee, 2018, The Role of Vitamin E in Immunity, Nutrients, 10, 10.3390/nu10111614

Lee, 1999, d-Alpha-tocopherol prevents the hyperglycemia induced activation of diacylglycerol (DAG)-protein kinase C (PKC) pathway in vascular smooth muscle cell by an increase of DAG kinase activity, Diabetes Res. Clin. Pract., 45, 183, 10.1016/S0168-8227(99)00048-0

Lee, 2009, Reactive oxygen species facilitate adipocyte differentiation by accelerating mitotic clonal expansion, J. Biol. Chem., 284, 10601, 10.1074/jbc.M808742200

Lee, 2010, Adipose tissue remodeling in pathophysiology of obesity, Curr. Opin. Clin. Nutr. Metab. Care, 13, 371, 10.1097/MCO.0b013e32833aabef

Lee, 2019, Peroxiredoxin 6 Confers Protection Against Nonalcoholic Fatty Liver Disease Through Maintaining Mitochondrial Function, Antioxid. Redox Signal, 31, 387, 10.1089/ars.2018.7544

Lenoir, 2017, Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic Glomerular Microvascular Injuries, J. Diabetes Res., 2017, 9603924, 10.1155/2017/9603924

Leopoldini, 2010, On the inhibitor effects of bergamot juice flavonoids binding to the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme, J. Agric. Food Chem., 58, 10768, 10.1021/jf102576j

Lettieri-Barbato, 2019, Redox control of non-shivering thermogenesis, Mol. Metab., 25, 11, 10.1016/j.molmet.2019.04.002

Lewis, 2019, Regulatory role of vitamin E in the immune system and inflammation, IUBMB Life, 71, 487, 10.1002/iub.1976

Li, 2008, Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance, Diabetes, 57, 1526, 10.2337/db07-1764

Li, 2018, (-)-Epigallocatechin-3-gallate (EGCG) inhibits starch digestion and improves glucose homeostasis through direct or indirect activation of PXR/CAR-mediated phase II metabolism in diabetic mice, Food Funct., 9, 4651, 10.1039/C8FO01293H

Libby, 2006, Inflammation and cardiovascular disease mechanisms, Am. J. Clin. Nutr., 83, 456S, 10.1093/ajcn/83.2.456S

Lin, 2008, Effects of cysteine-containing compounds on biosynthesis of triacylglycerol and cholesterol and anti-oxidative protection in liver from mice consuming a high-fat diet, Br. J. Nutr., 99, 37, 10.1017/S0007114507793881

Lin, 2016, Adipose extracellular matrix remodelling in obesity and insulin resistance, Biochem. Pharmacol., 119, 8, 10.1016/j.bcp.2016.05.005

Lira, 2011, Supplementing alpha-tocopherol (vitamin E) and vitamin D3 in high fat diet decrease IL-6 production in murine epididymal adipose tissue and 3T3-L1 adipocytes following LPS stimulation, Lipids Health Dis., 10, 37, 10.1186/1476-511X-10-37

Lone, 2016, Curcumin induces brown fat-like phenotype in 3T3-L1 and primary white adipocytes, J. Nutr. Biochem., 27, 193, 10.1016/j.jnutbio.2015.09.006

Ma, 2016, N-acetylcysteine Protects Mice from High Fat Diet-induced Metabolic Disorders, Pharm. Res., 33, 2033, 10.1007/s11095-016-1941-1

Maeda, 2005, Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues, Biochem. Biophys. Res. Commun., 332, 392, 10.1016/j.bbrc.2005.05.002

Makhoul, 2011, Associations of obesity with triglycerides and C-reactive protein are attenuated in adults with high red blood cell eicosapentaenoic and docosahexaenoic acids, Eur. J. Clin. Nutr., 65, 808, 10.1038/ejcn.2011.39

Manna, 2015, Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies, Metab. Syndr. Relat. Disord., 13, 423, 10.1089/met.2015.0095

Martinez de Lizarrondo, 2017, Potent Thrombolytic Effect of N-Acetylcysteine on Arterial Thrombi, Circulation, 136, 646, 10.1161/CIRCULATIONAHA.117.027290

Martin-Nizard, 1998, Alpha-tocopherol but not beta-tocopherol inhibits thrombin-induced PKC activation and endothelin secretion in endothelial cells, J. Cardiovasc. Risk, 5, 339, 10.1177/174182679800500510

McKenna, 2006, N-acetylcysteine attenuates the decline in muscle Na+,K+-pump activity and delays fatigue during prolonged exercise in humans, J. Physiol., 576, 279, 10.1113/jphysiol.2006.115352

McMurray, 2016, Reactive Oxygen Species and Oxidative Stress in Obesity-Recent Findings and Empirical Approaches, Obes. (Silver Spring), 24, 2301, 10.1002/oby.21654

Mehmeti, 2014, Peroxiredoxin 4 improves insulin biosynthesis and glucose-induced insulin secretion in insulin-secreting INS-1E cells, J. Biol. Chem., 289, 26904, 10.1074/jbc.M114.568329

Mehmetoglu, 2011, Correlation between vitamin A, E, coenzyme Q(10) and degree of insulin resistance in obese and non-obese subjects, J. Clin. Biochem. Nutr., 49, 159, 10.3164/jcbn.11-08

Miao, 2009, Regulation of superoxide dismutase genes: implications in disease, Free Radic. Biol. Med., 47, 344, 10.1016/j.freeradbiomed.2009.05.018

Mittendorfer, 2009, Relationship between body fat mass and free fatty acid kinetics in men and women, Obes. (Silver Spring), 17, 1872, 10.1038/oby.2009.224

Mohammed, 2018, Systems and WBANs for Controlling Obesity, J. Healthc. Eng., 2018, 1564748, 10.1155/2018/1564748

Mokhtari, 2017, A Review on Various Uses of N-Acetyl Cysteine, Cell J., 19, 11, 10.22074/cellj.2016.4872

Moncada, 1979, The role of prostacyclin in vascular tissue, Fed. Proc., 38, 66

Montonen, 2004, Dietary antioxidant intake and risk of type 2 diabetes, Diabetes Care, 27, 362, 10.2337/diacare.27.2.362

Moran, 2018, Intrinsic and Extrinsic Factors Impacting Absorption, Metabolism, and Health Effects of Dietary Carotenoids, Adv. Nutr., 9, 465, 10.1093/advances/nmy025

Munzel, 2017, Impact of Oxidative Stress on the Heart and Vasculature: Part 2 of a 3-Part Series, J. Am. Coll. Cardiol., 70, 212, 10.1016/j.jacc.2017.05.035

Murer, 2014, Antioxidant supplements reduced oxidative stress and stabilized liver function tests but did not reduce inflammation in a randomized controlled trial in obese children and adolescents, J. Nutr., 144, 193, 10.3945/jn.113.185561

Musolino, 2019, The effect of bergamot polyphenolic fraction on lipid transfer protein system and vascular oxidative stress in a rat model of hyperlipemia, Lipids Health Dis., 18, 115, 10.1186/s12944-019-1061-0

Musolino, 2020, Bergamot Polyphenols Improve Dyslipidemia and Pathophysiological Features in a Mouse Model of Non-Alcoholic Fatty Liver Disease, Sci. Rep., 10, 2565, 10.1038/s41598-020-59485-3

Nakashima, 1998, Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse, Arterioscler. Thromb. Vasc. Biol., 18, 842, 10.1161/01.ATV.18.5.842

Nath, 2006, Heme oxygenase-1: a provenance for cytoprotective pathways in the kidney and other tissues, Kidney Int., 70, 432, 10.1038/sj.ki.5001565

Niki, 2015, Evidence for beneficial effects of vitamin E, Korean J. Intern Med., 30, 571, 10.3904/kjim.2015.30.5.571

Ollinger, 2005, Bilirubin: a natural inhibitor of vascular smooth muscle cell proliferation, Circulation, 112, 1030, 10.1161/CIRCULATIONAHA.104.528802

Oyewole, 2015, Mitochondria-targeted antioxidants, FASEB J., 29, 4766, 10.1096/fj.15-275404

Pacifici, 2014, Peroxiredoxin 6, a novel player in the pathogenesis of diabetes, Diabetes, 63, 3210, 10.2337/db14-0144

Pae, 2009, Heme oxygenase-1: its therapeutic roles in inflammatory diseases, Immune Netw., 9, 12, 10.4110/in.2009.9.1.12

Pae, 2004, Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production, J. Immunol., 172, 4744, 10.4049/jimmunol.172.8.4744

Paine, 2010, Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential, Biochem. Pharmacol., 80, 1895, 10.1016/j.bcp.2010.07.014

Patrick, 2001, Cardiovascular disease: C-reactive protein and the inflammatory disease paradigm: HMG-CoA reductase inhibitors, alpha-tocopherol, red yeast rice, and olive oil polyphenols, A. Rev. Literature Altern. Med. Rev., 6, 248

Perkins, 2015, Peroxiredoxins: guardians against oxidative stress and modulators of peroxide signaling, Trends Biochem. Sci., 40, 435, 10.1016/j.tibs.2015.05.001

Perriotte-Olson, 2016, Nanoformulated copper/zinc superoxide dismutase reduces adipose inflammation in obesity, Obes. (Silver Spring), 24, 148, 10.1002/oby.21348

Peterson, 2019, Positive Effects of Heme Oxygenase Upregulation on Adiposity and Vascular Dysfunction: Gene Targeting vs. Pharmacologic Therapy, Int. J. Mol. Sci., 20, 10.3390/ijms20102514

Peterson, 2020, The Effects of Heme Oxygenase Upregulation on Obesity and the Metabolic Syndrome, Antioxid. Redox Signal, 32, 1061, 10.1089/ars.2019.7954

Poss, 1997, Heme oxygenase 1 is required for mammalian iron reutilization, Proc. Natl. Acad. Sci. U.S.A., 94, 10919, 10.1073/pnas.94.20.10919

Pratt, 2019, Mechanistic Insight of Na/K-ATPase Signaling and HO-1 into Models of Obesity and Nonalcoholic Steatohepatitis, Int. J. Mol. Sci., 21, 10.3390/ijms21010087

Randle, 1965, The glucose fatty acid cycle in obesity and maturity onset diabetes mellitus, Ann. N. Y. Acad. Sci., 131, 324, 10.1111/j.1749-6632.1965.tb34800.x

Rao, 1970, Effect of curcumin on serum and liver cholesterol levels in the rat, J. Nutr., 100, 1307, 10.1093/jn/100.11.1307

Ray, 2016, Obesity: An Immunometabolic Perspective, Front. Endocrinol. (Lausanne), 7, 10.3389/fendo.2016.00157

Rhee, 2012, Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides, J. Biol. Chem., 287, 4403, 10.1074/jbc.R111.283432

Rhee, 2016, Overview on Peroxiredoxin, Mol. Cells, 39, 1, 10.14348/molcells.2016.2368

Richie, 2015, Randomized controlled trial of oral glutathione supplementation on body stores of glutathione, Eur. J. Nutr., 54, 251, 10.1007/s00394-014-0706-z

Rizvi, 2014, The role of vitamin e in human health and some diseases, Sultan Qaboos Univ. Med. J., 14, e157

Rodriguez-Cuenca, 2010, Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice, Free Radic. Biol. Med., 48, 161, 10.1016/j.freeradbiomed.2009.10.039

Sakai, 2009, Inhibitory effect of carotenoids on the degranulation of mast cells via suppression of antigen-induced aggregation of high affinity IgE receptors, J. Biol. Chem., 284, 28172, 10.1074/jbc.M109.001099

Samuni, 2010, Inhibition of adipogenesis by Tempol in 3T3-L1 cells, Free Radic. Biol. Med., 49, 667, 10.1016/j.freeradbiomed.2010.05.028

Samuni, 2013, The chemistry and biological activities of N-acetylcysteine, Biochim. Biophys. Acta, 1830, 4117, 10.1016/j.bbagen.2013.04.016

Schett, 2008, The p38 mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis, Ann. Rheum. Dis., 67, 909, 10.1136/ard.2007.074278

Schmitt, 2015, Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study, Redox Biol., 6, 198, 10.1016/j.redox.2015.07.012

Schugar, 2017, The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue, Cell Rep., 19, 2451, 10.1016/j.celrep.2017.05.077

Schwarz, 1997, Retinoic acid blocks adipogenesis by inhibiting C/EBPbeta-mediated transcription, Mol. Cell Biol., 17, 1552, 10.1128/MCB.17.3.1552

Seddon, 2007, Oxidative stress and redox signalling in cardiac hypertrophy and heart failure, Heart, 93, 903, 10.1136/hrt.2005.068270

Shen, 2018, Early intervention of N-acetylcysteine better improves insulin resistance in diet-induced obesity mice, Free Radic. Res., 52, 1296, 10.1080/10715762.2018.1447670

Siersbaek, 2010, PPARgamma in adipocyte differentiation and metabolism–novel insights from genome-wide studies, FEBS Lett., 584, 3242, 10.1016/j.febslet.2010.06.010

Singh, 1995, Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected], J. Biol. Chem., 270, 24995, 10.1074/jbc.270.42.24995

Sirico, 2018, Effects of Physical Exercise on Adiponectin, Leptin, and Inflammatory Markers in Childhood Obesity: Systematic Review and Meta-Analysis, Child Obes., 14, 207, 10.1089/chi.2017.0269

Smith, 2016, Treatment of nonalcoholic fatty liver disease: role of AMPK, Am. J. Physiol. Endocrinol. Metab., 311, E730, 10.1152/ajpendo.00225.2016

Soderberg, 1999, Leptin is associated with increased risk of myocardial infarction, J. Intern Med., 246, 409, 10.1046/j.1365-2796.1999.00571.x

Sodhi, 2015, pNaKtide inhibits Na/K-ATPase reactive oxygen species amplification and attenuates adipogenesis, Sci. Adv., 1, e1500781, 10.1126/sciadv.1500781

Sodhi, 2015, Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet, PloS One, 10, e0128648, 10.1371/journal.pone.0128648

Sorrenti, 2019, Beneficial Effects of Pomegranate Peel Extract and Probiotics on Pre-adipocyte Differentiation, Front. Microbiol., 10, 10.3389/fmicb.2019.00660

Sparkenbaugh, 2015, Excess of heme induces tissue factor-dependent activation of coagulation in mice, Haematologica, 100, 308, 10.3324/haematol.2014.114728

Springer, 2019, Resveratrol and Its Human Metabolites-Effects on Metabolic Health and Obesity, Nutrients, 11, 10.3390/nu11010143

Srikanthan, 2016, Systematic Review of Metabolic Syndrome Biomarkers: A Panel for Early Detection, Management, and Risk Stratification in the West Virginian Population, Int. J. Med. Sci., 13, 25, 10.7150/ijms.13800

Stolarczyk, 2017, Adipose tissue inflammation in obesity: a metabolic or immune response, Curr. Opin. Pharmacol., 37, 35, 10.1016/j.coph.2017.08.006

Straub, 2019, Antioxidants protect against diabetes by improving glucose homeostasis in mouse models of inducible insulin resistance and obesity, Diabetologia, 62, 2094, 10.1007/s00125-019-4937-7

Sun, 2011, Adipose tissue remodeling and obesity, J. Clin. Invest., 121, 2094, 10.1172/JCI45887

Sun, 2013, Fibrosis and adipose tissue dysfunction, Cell Metab., 18, 470, 10.1016/j.cmet.2013.06.016

Sun, 2019, Clinical efficacy of acetylcysteine combined with tetrandrine tablets in the treatment of silicosis and the effect on serum IL-6 and TNF-alpha, Exp. Ther. Med., 18, 3383, 10.3892/etm.2019.7966

Takamiya, 2002, Stabilization of mast cells by heme oxygenase-1: an anti-inflammatory role, Am. J. Physiol. Heart Circ. Physiol., 283, H861, 10.1152/ajpheart.00740.2001

Talasaz, 2013, N-Acetylcysteine effects on transforming growth factor-beta and tumor necrosis factor-alpha serum levels as pro-fibrotic and inflammatory biomarkers in patients following ST-segment elevation myocardial infarction, Drugs R. D., 13, 199, 10.1007/s40268-013-0025-5

Thalhamer, 2008, MAPKs and their relevance to arthritis and inflammation, Rheumatol. (Oxford), 47, 409, 10.1093/rheumatology/kem297

Thompson, 2007, Treatment of obesity, Mayo Clin. Proc., 82, 93, 10.1016/S0025-6196(11)60971-3

Thong-Ngam, 2007, N-acetylcysteine attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis, World J. Gastroenterol., 13, 5127, 10.3748/wjg.v13.i38.5127

Tran, 1990, R,R,R-alpha-tocopherol potentiates prostacyclin release in human endothelial cells. Evidence for structural specificity of the tocopherol molecule, Biochim. Biophys. Acta, 1043, 189, 10.1016/0005-2760(90)90295-9

Unal, 2010, Matrix metalloproteinase-9 is increased in obese subjects and decreases in response to pioglitazone, J. Clin. Endocrinol. Metab., 95, 2993, 10.1210/jc.2009-2623

Upston, 2003, The role of vitamin E in atherosclerosis, Prog. Lipid Res., 42, 405, 10.1016/S0163-7827(03)00024-9

von Lintig, 2012, Provitamin A metabolism and functions in mammalian biology, Am. J. Clin. Nutr., 96, 1234S, 10.3945/ajcn.112.034629

Wagner, 2017, HO-1 inhibits preadipocyte proliferation and differentiation at the onset of obesity via ROS dependent activation of Akt2, Sci. Rep., 7, 40881, 10.1038/srep40881

Wallace, 2001, Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS), Circulation, 104, 3052, 10.1161/hc5001.101061

Wallert, 2014, Regulatory metabolites of vitamin E and their putative relevance for atherogenesis, Redox Biol., 2, 495, 10.1016/j.redox.2014.02.002

Wang, 2007, Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport in lipoproteins in age-related macular degeneration, Am. J. Clin. Nutr., 85, 762, 10.1093/ajcn/85.3.762

Wang, 2009, The heme oxygenase-1/carbon monoxide pathway suppresses TLR4 signaling by regulating the interaction of TLR4 with caveolin-1, J. Immunol., 182, 3809, 10.4049/jimmunol.0712437

Wang, 2009, Curcumin, a potential inhibitor of up-regulation of TNF-alpha and IL-6 induced by palmitate in 3T3-L1 adipocytes through NF-kappaB and JNK pathway, BioMed. Environ. Sci., 22, 32, 10.1016/S0895-3988(09)60019-2

Wang, 2011, ROS-activated p38 MAPK/ERK-Akt cascade plays a central role in palmitic acid-stimulated hepatocyte proliferation, Free Radic. Biol. Med., 51, 539, 10.1016/j.freeradbiomed.2011.04.019

Wang, 2013, Oxidative stress response elicited by mitochondrial dysfunction: implication in the pathophysiology of aging, Exp. Biol. Med. (Maywood), 238, 450, 10.1177/1535370213493069

Wang, 2016, The protection conferred against ischemia-reperfusion injury in the diabetic brain by N-acetylcysteine is associated with decreased dicarbonyl stress, Free Radic. Biol. Med., 96, 89, 10.1016/j.freeradbiomed.2016.03.038

Wegiel, 2012, Go green: the anti-inflammatory effects of biliverdin reductase, Front. Pharmacol., 3, 10.3389/fphar.2012.00047

Wensveen, 2015, The “Big Bang” in obese fat: Events initiating obesity-induced adipose tissue inflammation, Eur. J. Immunol., 45, 2446, 10.1002/eji.201545502

Widjaja, 2019, Hypercoagulable State and Glycemic Control in Diabetic Patients with Malignancy, Open Access Maced J. Med. Sci., 7, 4066, 10.3889/oamjms.2019.860

Wiseman, 1995, Comparison of the effects of dietary vitamin E on in vivo and in vitro parameters of lipid peroxidation in the rabbit, Free Radic. Biol. Med., 19, 617, 10.1016/0891-5849(95)00078-C

Wong, 2017, Vitamin E As a Potential Interventional Treatment for Metabolic Syndrome: Evidence from Animal and Human Studies, Front. Pharmacol., 8, 10.3389/fphar.2017.00444

Wood Dos Santos, 2018, Effects of Polyphenols on Thermogenesis and Mitochondrial Biogenesis, Int. J. Mol. Sci., 19, 10.3390/ijms19092757

Wood, 2003, Structure, mechanism and regulation of peroxiredoxins, Trends Biochem. Sci., 28, 32, 10.1016/S0968-0004(02)00003-8

Wu, 2007, Effects of alpha-tocopherol and mixed tocopherol supplementation on markers of oxidative stress and inflammation in type 2 diabetes, Clin. Chem., 53, 511, 10.1373/clinchem.2006.076992

Wu, 2019, Heme Catabolic Pathway in Inflammation and Immune Disorders, Front. Pharmacol., 10, 10.3389/fphar.2019.00825

Yamada, 2018, Peroxiredoxin 4 (PRDX4): Its critical in vivo roles in animal models of metabolic syndrome ranging from atherosclerosis to nonalcoholic fatty liver disease, Pathol. Int., 68, 91, 10.1111/pin.12634

Zaragoza, 2000, Effect of N-acetylcysteine and deferoxamine on endogenous antioxidant defense system gene expression in a rat hepatocyte model of cocaine cytotoxicity, Biochim. Biophys. Acta, 1496, 183, 10.1016/S0167-4889(00)00036-7

Zelko, 2002, Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression, Free Radic. Biol. Med., 33, 337, 10.1016/S0891-5849(02)00905-X

Zhang, 2018, Epigallocatechin gallate improves insulin resistance in HepG2 cells through alleviating inflammation and lipotoxicity, Diabetes Res. Clin. Pract., 142, 363, 10.1016/j.diabres.2018.06.017

Zicha, 2006, Antihypertensive mechanisms of chronic captopril or N-acetylcysteine treatment in L-NAME hypertensive rats, Hypertens. Res., 29, 1021, 10.1291/hypres.29.1021