## 1 Introduction  
The current obesity pandemic is a significant public health issue, affecting one-third of the global adult population. Obesity, body mass index (BMI) \(\geq\) 30 kg/m\({}^{2}\), is associated with an increased risk of several diseases such as insulin resistance (IR), the central feature of type 2 diabetes (T2D). IR results in deficient glucose homeostasis and altered mitochondrial oxidative capacity. SM is a major regulator of glucose homeostasis and SM dysfunction is a primary component of obesity-induced IR [1, 2]. During obesity, nutritional excess due to dietary fat intake is associated with dyslipidemia and ectopic fat accumulation in SM. SM IR strongly correlates with intramyocellular lipid content [3]. The increased availability of intramyocellular lipids represents an excess of fuel stimulating SM mitochondrial activity. Consequently, oxidative phosphorylation increases, inducing higher reactive oxygen species (ROS) production and emission [3]. The increase in mitochondrial ROS is one of the early events leading to SM dysfunction and to IR and T2D [4]. Under physiological conditions, ROS are essential intracellular signalers and the dynamic balance between ROS production and antioxidant defense systems maintains cellular redox homeostasis. Thus, mitochondria are critical organelles and preserving both their quantity and activity is essential for maintaining muscle metabolic homeostasis [5] and muscle health [6]. During obesity, lipid overload overwhelms mitochondrial activity [3; 7], leading to lipid accumulation and higher ROS production that surpass the capacity of antioxidant defenses for their neutralization. This imbalance favors alteration in redox homeostasis and muscle metabolism, harming cellular components and impairing their functions [8; 9]. ROS-induced modifications include peroxidation of polyunsaturated membrane lipids and formation of 4-hydroxy-2-nonenal aldehyde (4-HNE), which binds DNA, lipids and proteins, thereby inducing their dysfunction. Mitochondrial polyunsaturated membrane lipids are the primary target of ROS attack [10]. This leads to mitochondrial alteration, characterized by reduced activity of citrate synthase (CS)--a pivotal enzyme in the citric acid cycle--and cytochrome c oxidase subunit IV (CoxIV), an integral part of the mitochondrial electron transport chain [3; 7]. These alterations associated with lipid overload result in disruption of signaling cascades and IR development [11]. The nuclear factor erythroid 2-related factor 2 (Nrf2) molecular pathway is crucial for suppressing oxidative stress and restoring homeostasis. The transcriptional factor Nrf2 is the final effector of a cellular pathway activated by the phosphorylation of the ubiquitin-binding protein p62 at serine 349 (P-p62). In fact, P-p62 interacts with the Nrf2 inhibitor, the Kelch-like ECH-associated protein 1 (Keap1), culminating in its degradation by the proteasome and provoking translocation of Nrf2 to the nucleus and transcription of its target genes [12]. Nrf2 promotes the expression of antioxidant enzymes such as heme-oxygenase 1 (HO-1), catalase and superoxide dismutases (SODs) [13]. Importantly, it has recently been shown that HO-1 could regulate mitochondrial functions and biogenesis during exercise and nutritional stress and drive insulin sensitivity [14; 15]. Thus, the Nrf2 pathway has emerged as a master regulator of redox metabolism and a central mechanism for controlling and protecting mitochondrial metabolism [16]. Tackling obesity and SM IR requires significant lifestyle modifications like exercise and dietary changes. However, maintaining these behavioral modifications for the long-term can be challenging, inducing consideration of medications and surgery despite their associated side effects and post-surgery risks. The pressing need for new strategies to prevent and treat obesity and IR has prompted exploration of alternative approaches.