Table 1.

Summary of mechanistic action of antioxidants in ameliorating obesity phenotype and associated comorbidities.

Antioxidant	Source	Pathway/Mechanism	Anti-Obesity Phenotype and Related Comorbidities	References
Peroxiredoxin	Endogenous Enzyme	Inhibition of PPARγ and C/EBPα	Adiponectin Insulin sensitivity Adipogenesis Protein carbonylation	(Huh et al., 2012; Mehmeti et al., 2014; Pacifici et al., 2014; Hammarstedt et al., 2018; Kim et al., 2018; Yamada and Guo, 2018; Lee et al., 2019; Kim et al., 2020)
		Phosphorylation of AMPK	Fatty acid oxidation SREBP-1 FAS Lipid accumulation
		Inhibition of IL-6, IL-10, and TNFα	Insulin secretion Diabetes Dyslipidemia
N-Acetylcysteine	Over-the-counter oral supplement	Inhibition of PPARγ and C/EBPβ	Lipolysis Adipogenesis NAFLD/NASH	(Girouard et al., 2003; McKenna et al., 2006; Carlsen et al., 2009; Calzadilla et al., 2011; Haleagrahara et al., 2011; Schmitt et al., 2015; Ma et al., 2016; Pratt et al., 2019; Sun et al., 2019)
		Inhibition of NFkB	Insulin sensitivity Inflammatory cascades
		Promotes skeletal muscle Na+/K+ ATPase activity	Motor activity
		Activates cardiac Superoxide dismutase and glutathione	Cardiac efficiency Cardiac fibrosis
		Upregulates platelet glutathione and Nitric Oxide	Vasodilation Thrombogenicity
		Downregulates malic enzyme and fatty acid synthase	Lipogenesis Cholesterologenesis
		Destabilizes Von Willebrand Factor	Thrombogenicity
Vitamin E	Vegetable oils, wheatgerm, sunflower, soybean, walnut, over-the-counter oral supplement	Downregulates IL-6, TNF-α, malondialdehyde and c- reactive protein	Insulin sensitivity Inflammatory cascades	(Boscoboinik et al., 1991; Cook-Mills, 2013; Alcala et al., 2015; Lin et al., 2016; Wong et al., 2017; Lee and Han, 2018)
		Inhibition of p38 MAPK pathways	Insulin sensitivity Adipogenesis Inflammatory cascades Oxidative cascades Collagen deposition and fibrosis
		Upregulates M2 macrophage phenotype	Inflammatory response
		Inhibition of PKC pathways	Vascular disease Thrombogenicity Inflammatory cascades
		Upregulates nitric oxide synthase and prostacyclins	Vasodilation
		Downregulates LDL, HDL and cholesterologenesis	Lipid Mobilization Vascular disease Hepatic steatosis
		Downregulates ICAM-1 and VCAM-1	Vascular disease Thrombogenicity
		Downregulates Matrix Metalloproteinases	Adipocyte expansion Insulin sensitivity Inflammatory response
Heme Oxygenase–1	Endogenous enzyme	Degrades free heme	Liberation of CO and Biliverdin Inflammatory response Oxidative cascades	(Burgess et al., 2010; Gozzelino et al., 2010; Chan et al., 2011; Cao et al., 2012; Sodhi et al., 2015; Peterson et al., 2020)
		Inhibits MAPK, NF-kβ, PKC	Vasodilation Inflammatory response Adipogenesis Thrombogenicity
		Upregulates ferritin synthesis	Inflammatory response
		Inhibition of PPARγ and C/EBPα	Lipolysis Adipogenesis
		Downregulates TNF-α, IL-1β, IL-2	Insulin sensitivity Inflammatory response
		Upregulates adiponectin	Insulin sensitivity Inflammatory response Adipogenesis
		Reduces oxidized LDL, VCAM-1, mast cell degranulation	Vascular disease Inflammatory response
		Upregulates AMPK cascades	Lipid Mobilization Insulin sensitivity Vascular disease Hepatic steatosis Lipogenesis
		Activates soluble guanylyl cyclase	Vasodilation Thrombogenicity
Polyphenol	Cranberry, red wine, green tea, pomegranate extract, curcumin, bergamot	Deacetylation of PGC1α	Mitochondrial Biogenesis Lipid Mobilization Energy expenditure	(Lagouge et al., 2006; Houtkooper et al., 2012; Fraga et al., 2019; Springer and Moco, 2019)
		Inhibition of PPARγ and SIRT1	Lipolysis Adipogenesis
		Activation of Nuclear factor-erythroid 2-related factor-2 (Nrf2)	Superoxide dismutase Body Mass Index Blood pressure Weight
Carotenoids	Red, yellow, and orange fruits and vegetables	Inhibition of PPARγ	Adipogenesis	(Schwarz et al., 1997; Maeda et al., 2005; Langi et al., 2018)
		Upregulates uncoupling protein-1 (UCP-1) and β3-adrenergic receptor (Adrb3)	Thermogenesis Lipid Mobilization Energy expenditure Weight loss
Superoxide Dismutase	Endogenous Enzyme	Inhibition of PPARγ, PPARα, FIAF	Lipolysis Adipogenesis	(Hennig et al., 2006; Samuni et al., 2010; Perriotte-Olson et al., 2016)
		Decreases levels of Carnitine Palmitoyl Transferase and Fatty Acid Synthase	Lipogenesis
		Inhibition of ERK1/2 and NF-κB	Inflammatory cascades

This table summarizes the source of each antioxidant along with the mechanism that is modulated with the supplementation of each antioxidant. The mechanistic action of each antioxidant results in amelioration of obesity phenotype and characteristics associated with it. The green arrow () represents upregulation and red arrow () represents downregulation of phenotypical characteristics of obesity in response to antioxidants.