Obesity is associated with severe metabolic diseases such as type 2 diabetes, insulin resistance, cardiovascular disease and some forms of cancer. The pathophysiology of obesity-induced metabolic diseases has been strongly related to white adipose tissue (WAT) dysfunction through several mechanisms such as fibrosis, apoptosis, inflammation, ER and oxidative stress. However, little is known of whether these processes are also present in brown adipose tissue (BAT) during obesity, and the potential consequences on mitochondrial activity. Here we characterized the BAT of obese and hyperglycemic mice treated with a high-fat diet (HFD) for 20 weeks. The hypertrophic BAT from obese mice showed no signs of fibrosis nor apoptosis, but higher levels of inflammation, ER stress, ROS generation and antioxidant enzyme activity than the lean counterparts. The response was attenuated compared with obesity-induced WAT derangements, which suggests that BAT is more resistant to the obesity-induced insult. In fact, mitochondrial respiration in BAT from obese mice was enhanced, with a 2-fold increase in basal oxygen consumption, through the upregulation of complex III of the electron transport chain and UCP1. Altogether, our results show that obesity is accompanied by an increase in BAT mitochondrial activity, inflammation and oxidative damage.

Objective: To test whether enhancing the capability of adipose tissue to store lipids using antioxidant supplementation may prevent the lipotoxic effects and improve the metabolic profile of long‐term obesity.Methods: C57BL/6J mice were randomized into three experimental groups for 28 weeks: control group (n = 10) fed chow diet (10% kcal from fat), obese group (O, n = 12) fed high‐fat (HF) diet (45% kcal from fat), and obese group fed HF diet and supplemented twice a week with 150 mg of α‐tocopherol (vitamin E) by oral gavage (OE, n = 12).Results: HF diet resulted in an obese phenotype with a marked insulin resistance, hypertriglyceridemia, and hepatic steatosis in O mice. Histological analysis of obese visceral adipose tissue (VAT) revealed smaller adipocytes surrounded by a fibrotic extracellular matrix and an increased macrophage infiltration, with the consequent release of proinflammatory cytokines. Vitamin E supplementation decreased oxidative stress and reduced collagen deposition in the VAT of OE mice, allowing a further expansion of the adipocytes and increasing the storage capability. As a result, circulating cytokines were reduced and hepatic steasosis, hypertriglyceridemia, and insulin sensitivity were improved.Conclusions: Our results suggest that oxidative stress is implicated in extracellular matrix remodeling and may play an important role in metabolic regulation.

Brown adipose tissue (BAT) dissipates energy to produce heat. Thus, it has the potential to regulate body temperature by thermogenesis. For the last decade, BAT has been in the spotlight due to its rediscovery in adult humans. This is evidenced by over a hundred clinical trials that are currently registered to target BAT as a therapeutic tool in the treatment of metabolic diseases, such as obesity or diabetes. The goal of most of these trials is to activate the BAT thermogenic program via several approaches such as adrenergic stimulation, natriuretic peptides, retinoids, capsinoids, thyroid hormones, or glucocorticoids. However, the impact of BAT activation on total body energy consumption and the potential effect on weight loss is still limited. Other studies have focused on increasing the mass of thermogenic BAT. This can be relevant in obesity, where the activity and abundance of BAT have been shown to be drastically reduced. The aim of this review is to describe pathological processes associated with obesity that may influence the correct differentiation of BAT, such as catecholamine resistance, inflammation, oxidative stress, and endoplasmic reticulum stress. This will shed light on the thermogenic potential of BAT as a therapeutic approach to target obesity-induced metabolic diseases.

Although a high intake of antioxidants may decrease the risk of developing cardiovascular diseases, under certain circunstances they may promote free radical generation and lipid peroxidation. The objectives of the present study were to determine the antioxidant effects of ascorbic acid (AA), dehydroascorbic acid (DHA) and flavonoids on LDL submitted to different degrees of oxidation. LDL was submitted to oxidation with CuCl₂ (2.4 μM). Before or at different times after the propagation of the oxidation process, 28 μM (5 μg/ml) of either AA or DHA or 5 μg/mL flavonoids extract were added. Alpha-tocopherol, conjugated dienes, thiobarbituric acid reacting substances (TBARS) and LDL electrophoretic mobility were determined as indices of LDL oxidation. The presence of any of the three antioxidants from the onset of the incubation delayed the oxidation process. However, the addition of both DHA and flavonoids to the oxidation process when it was already initiated and alpha-tocopherol consumed, accelerated the oxidation. In contrast, AA delayed the oxidation process even when added after alpha-tocopherol was consumed. Nevertheless, it also accelerated LDL oxidation when added during the propagation phase of the oxidation process. In conclusion: although AA, DHA and flavonoids delay LDL oxidation when added before the initiation of the process, they accelerate the process if added to minimally oxidized LDL.