**1. Introduction**

Since 1998, the National Institutes of Health (NIH) has recognized obesity as a disease due to the impact of individuals' health on society and the high economic and social costs incurred [1]. There is an adjacent link between obesity and metabolic disorders, including Alzheimer's disease, respiratory problems, cardiovascular disease (CVD), type 2 diabetes (T2D), cancer, and non-alcoholic fatty liver disease (NAFLD) [2]. Body mass index (BMI) ≥ 30 has been accepted in many studies as one of the critical indicators of obesity. Still, this index is less valid than measuring the waist-to-hip ratio (WHR) due to the inability to count the lean body mass (LBM) [3].

Obesity is the result of overconsumption of nutrients and a sedentary lifestyle. As the consumption of nutrients increases, an imbalance is created between energy intake and expenditure, leading to fat accumulation in adipose tissue (AT) and obesity [4]. The World Health Organization (WHO) estimates the number of obese people globally at 650 million [2]. Several studies have shown that obesity depends on the regional distribution of excess body fat, not excess body weight. Thus, one of the most critical risk factors for obesity and related diseases is abdominal fat, which leads to the stimulation of proinflammatory and pro-oxidant states [5], the overproduction of free radicals, and pursuant oxidative stress (OS) in AT [6].

Scientists have made several efforts to control this disease. Various treatment methods, such as medication, surgery, exercise, and diet, have been considered in this regard. However, control of the disease is still far from expected. Increasing energy expenditure and subsequent weight loss is a smart way to control and prevent obesity [7]. In this regard, although authoritative articles have approved anti-obesity drugs, such as orlistat, and the use of weight-loss surgeries, the use of these methods is associated with many side

**Citation:** Taherkhani, S.; Suzuki, K.; Ruhee, R.T. A Brief Overview of Oxidative Stress in Adipose Tissue with a Therapeutic Approach to Taking Antioxidant Supplements. *Antioxidants* **2021**, *10*, 594. https:// doi.org/10.3390/antiox10040594

Academic Editors: Gareth Davison and Conor McClean

Received: 5 March 2021 Accepted: 8 April 2021 Published: 13 April 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

effects [4]. Health researchers have identified diet, especially antioxidant supplements, as the most appropriate treatment for obesity [8]. Antioxidants affect the body's endocrine and metabolic functions, leading to increased exothermic process and energy expenditure to reduce OS and body weight and improve obesity [9].

In this study, we have reviewed the effect of antioxidant supplements on AT changes under OS. The authors have allocated the content of this review article to the introduction, sources, and tools for measuring reactive oxygen species (ROS) in AT, a brief description of AT and related disorders, and finally, the relationship between antioxidant supplementation and obesity, respectively.

#### **2. Overview of ROS**

Living organisms need oxygen (O2) molecules to survive on earth. Therefore, these molecules' presence is necessary to produce energy by the electron transfer chain (ETC) [10,11]. Under stressful conditions, O2 molecules in the body are converted into two separate atoms with unpaired electrons, named free radicals. These radicals are derived from O2 and are known as ROS [12]. ROS include superoxide anion (O2 •−), hydrogen peroxide (H2O2), and hydroxyl radical (OH. ), which play a vital role in causing pathophysiological damage, especially cellular damage to lipids, proteins, and deoxyribonucleic acid (DNA) [13–15]. When an unpaired electron is added to free radicals, O2 •− is formed. O2 •− has shown various behaviors in different environments. For example, in aqueous perimeters, this radical is reduced first to H2O2 by superoxide dismutase (SOD) and then converted to H2O and O2 by catalase (CAT). However, H2O2 may be converted to OH• in the presence of molecules containing ferrous iron (Fe2+) [16]. Various factors such as ROS concentration, time, and location of cells exposed to these species can determine the extent of these molecules' damage. ROS is not harmful in low to moderate concentrations and has beneficial effects on cellular responses and signaling, gene expression, regulation of muscle power fluctuations, mitogenic responses, apoptosis, and protection against infections [11,12]. On the other hand, OH. is highly reactive and harmful due to its very short half-life of only a few nanoseconds. Although H2O2 can be stable for a more extended period and does not damage cells, in higher concentrations, it has highly detrimental potency. H2O2 in aquatic environments, especially the human body, has a shorter half-life due to its neutralizing enzymes, which quickly cause irreparable damage to cells [17].

Since the discovery of ROS in 1970, most tissues in the body have been found to be affected by these reactive species, including cellular redox imbalance, OS, and cell dysfunction. ROS's breakdown and production imbalance cause OS to alter cell function by damaging various molecules in the body [18,19]. In addition to ROS, other reactive species such as reactive nitrogen (RNS) and sulfur species (RSS) are also known as free radicals, although they are not derived from O2 [20]. When nitric oxide (NO) is added to O2 •−, it creates a highly damaging radical named RNS that can cause the formation of peroxinitrate (ONOO−). This molecule causes nitrosative stress to various cells in the body [21]. When ROS is overproduced in the body, the antioxidant defense systems cannot eliminate or neutralize these species, and components such as proteins and lipids are damaged. Following this damage, pathological conditions such as vascular diseases (atherosclerosis, hypertension, and diabetes), respiratory disease, cell death, premature aging, neurological disorders, and degradation of skin enzymes (hyaluronidase and collagenase), platelet aggregation in vessels, and mutations and damage occur [22–25].

Many molecules play an essential role in maintaining the body's homeostasis. However, one of the most important natural products of metabolism is ROS, which participate in numerous cellular signaling pathways in the body. Of course, these products have few effects on the cellular system, but their excessive production may have irreversible effects on the body's various physiological systems [26]. The body uses endogenous antioxidant defenses against these molecules. However, in stressful situations, endogenous protection alone may not be enough to eliminate or neutralize ROS. In such cases, various exogenous factors such as diet, lifestyle, medication, and physical activity play an essential

role in maintaining ROS balance [27]. One of the tissues that are severely affected by ROS imbalance is AT. Under similar conditions, adipokines secreted by AT such as leptin and adiponectin increase and decrease, respectively [16]. ROS production in AT occurs due to excessive consumption of nutrients [20,23,28]. It is noteworthy that the hormone adiponectin acts as an anti-inflammatory hormone in AT. Since obesity is an inflammatory disease, this hormone's concentration in obesity decreases due to increased inflammatory cytokines. By reducing this hormone's expression in obese people, its influential role in improving insulin sensitivity also diminishes. As a result, obese people face a complication named insulin resistance (IR), which predisposes them to T2D [29].
