Beneficial effects of Ilex paraguariensis in the prevention of obesity‐associated metabolic disorders in mice

Abstract

Obesity is a chronic condition involving inflammation and oxidative stress that commonly predisposes affected individuals to develop metabolic disorders. We hypothesize that Ilex paraguariensis (IP) can modulate oxidative stress and inflammation underpinning metabolic disorders caused by obesity. C57BL/6 mice were fed a high‐fat diet (HFD group) for 12 weeks. Concomitantly, some mice were treated with roasted IP (15 mg/ml – HFD + IP) or dimethyl fumarate (DMF) as a positive control (2 mg/ml – HFD + DMF). The control group received standard chow and water ad libitum. Histological analyses of fat tissue and liver, and quantification of mediators related to oxidative stress (Kelch‐like ECH‐associated protein 1/NF‐E2‐related factor 2, NADP(H) quinone oxidoreductase‐1 [NQO1], heme oxygenase 1 [HO1], and superoxide dismutase) as well as metabolic profile blood biomarkers (glucose, leptin, resistin, high‐density lipoproteins [HDLs], and triglycerides) were performed. Metabolic disorders were prevented in mice treated with IP, as evidenced by the observation that glucose, HDL, and resistin levels were similar to those assessed in the control group. Morphological analyses showed that both IP and DMF treatments prevented hepatic steatosis and adipocyte hypertrophy in visceral adipose tissue. Finally, although the antioxidant response stimulated by IP was quite limited, significant effects were found on NQO1 and HO1 expression. In conclusion, IP has promising preventative effects on the development of metabolic disorders caused by obesity.

Nrf2 activation by hydroxytyrosol and dimethyl fumarate ameliorates skin tissue repair in high‐fat diet‐fed mice by promoting M2 macrophage polarization and normalizing inflammatory response and oxidative damage

“…These results might have associated with the dose and period of administration of these components since anti-obesogenic effects of HT or DMF are observed when doses higher than 20 mg/Kg for 12 weeks are administrated in obese animals. [10,11,39] In our study, obese animals were treated with therapeutical doses of HT or DMF (1 or 10 mg/Kg, respectively)…”

“…[ 40,41 ] Pharmacological Nrf2 activators, such as DMF approved of treating psoriasis and multiple sclerosis, are also able to reduce overweight and white fat mass in HDF‐fed animals. [ 10,16,42 ] On the contrary to HT, DMF directly stimulates electrophilic modification of Keap1‐Cys‐151 that promotes Nrf2 translocation to nuclei. [ 43 ] In this study, mice subjected to an HFD developed overweight, glucose resistance, hyperglycemia, dyslipidemia, gain of white fat, and hepatic steatosis, which is consistent with previous findings.…”

“…These results might have associated with the dose and period of administration of these components since anti‐obesogenic effects of HT or DMF are observed when doses higher than 20 mg/Kg for 12 weeks are administrated in obese animals. [ 10,11,39 ] In our study, obese animals were treated with therapeutical doses of HT or DMF (1 or 10 mg/Kg, respectively) proportional to doses for humans [ 19,20 ] for 2 weeks. In addition, DMF showed a higher efficiency in the reduction of some obesogenic parameters (such as hepatic steatosis, body weight, and hyperglycemia) when compared with HT, suggesting the higher efficiency of DMF in the activation of Nrf2 pathway.…”

“…[9] The administration of Nrf2 activators, such as hydroxytyrosol (HT) and dimethyl fumarate (DMF), is associated with a reduction of systemic inflammation and obesogenic parameters in HFD-fed animals. [10,11] HT is a polyphenol observed in olive oil and has a scavenger activity and directly activates Nrf2 signaling pathway promoting the production of heme oxygenase-1 (HO-1). [12,13] In addition, HT has other cytoprotective properties such as anticancer, anti-inflammatory, and anti-steatotic effects that have beneficial health effects.…”