The increase in life expectancy has led to a larger proportion of elderly women and a greater public health concern regarding the physiological changes related to the menopause and post-menopause. Nearly 40% of women seek treatment to minimize menopause-induced symptoms that include headaches, night sweats, vaginal dryness, and sleep disturbances (Nachtigall, 1998). An important clinical feature of menopause is the decline in ovarian produced hormones such as estrogen (Maltais et al., 2009), which is associated with several physiological changes such as increased risk of atherosclerosis (Schillaci et al., 1998), diabetes mellitus (Zois et al., 2009), bone loss (Kemmler et al., 2004), muscle loss (sarcopenia; 6), changes in body composition, altered lipid profiles, fat deposition (Kemmler et al., 2004; Brochu et al., 2009), and elevated inflammatory markers (Pfeilschifter et al., 2002). Together, the menopause caused alterations can lead to a metabolic syndrome characterized by the emergence and combination of at least 3 risk factors such as obesity, dyslipidemia, hyperglycemia, hyperinsulinemia, insulin resistance and hypertension (Eckel et al., 2005; Prasun, 2020; Yoneshiro et al., 2011).

Obesity induced by a reduction of estrogen production can cause systemic inflammation that can compromise mitochondrial functions and, consequently, reduce thermogenesis, which plays an important role in energy expenditure to maintain body temperature (Yoneshiro et al., 2011; Alberdi et al., 2013) and is mainly regulated by the sirtuin (SIRT1) pathway (Alberdi et al., 2013). Thermogenesis is believed to be dependent mainly on the activation of uncoupling proteins (UCPs), more specifically UCP1, located in the inner membrane of the mitochondria of brown adipose tissue (BAT). The activity of UCP1 uncouples the proton gradient (H+) used for the synthesis of adenosine triphosphate to generate a heat bioproduct (Tabuchi and Sul, 2021). Among the family of uncoupling proteins, UCP2 and UCP3 isoforms are also located in BAT, at lower levels, as well as in lung and muscle tissue although they do not appear to play an effective role in thermogenesis (Pohl et al., 2019). White adipose tissue (WAT) normally functions in whole-body metabolism and not thermoregulation (Heinonen et al., 2020). However, when the body is subjected to extreme situations (e.g., cold exposure), some WAT cells may undergo a process known as “browning”, which makes WAT cells phenotypically more like classic adipocytes in BAT with a higher of mitochondria and UCP1 (Bartelt and Heeren, 2014).

Currently, estrogen treatment is available for women who have menopause induced symptoms. However, known collateral effects of estrogen therapy include an increased risk for stroke, heart attack, blood clots and cancer (Marjoribanks et al., 2017; Ettinger et al., 2018; Mattar et al., 2008). To develop alternative, non-hormonal strategies to minimize deleterious metabolic effects, the scientific community has focused on the use of natural products that show promise to regulate lipid metabolism, satiety, adipogenesis and thermogenic effects (Lee et al., 2016; Madak-Erdogan et al., 2016; Tardivo et al., 2015), which may be repurposed for use in patients with metabolic syndromes caused by menopause. Recent interest has been emerging in an herb widely consumed mainly in South America, Ilex paraguariensis or yerba MATE (MATE) due to its known antioxidant (Matsumoto et al., 2009; Leonard et al., 2010) and cardioprotection effect (Cahuê et al., 2017). In addition, it is a potent modulating agent of energy metabolism that influences both glucose and lipid oxidation (Resende et al., 2012; Silva et al., 2011), which may explain its impact on adipogenesis and effectiveness as an effective adjuvant in weight loss (Gambero and Ribeiro, 2015). The adaptogenic effects of Ilex paraguariensis as an antioxidant agent and modulator of energy metabolism are closely linked to some of its components, namely, polyphenols, saponins and methylxanthines (Resende et al., 2012; Gosmann et al., 2012).

Although the literature demonstrates the improvement of energy metabolism in rats and humans treated with yerba MATE, there are few data available that evaluate the influence of this herb on the systemic changes resulting from menopause, specifically on adipose tissue, which is the main objective of this study. Here, we tested the effects of yerba MATE consumption in ovariectomized rats, a known model for estrogen depletion (Idris, 2012), and a significant reduction in weight gain was observed. Further analysis of the white adipose tissue showed that ingestion of MATE prevented adipogenesis as well as induced the browning process and the potential for thermogenesis.