Introduction
Over the past two decades, the increasing prevalence of metabolic syndrome (MetS) has emerged as a significant global public health issue. Currently, over one-third of adults meet the criteria for MetS [1]. More concerning, however, is a recent report indicating that less than 20% of U.S. adults are metabolically healthy [2]. Metabolic health is defined not only by the absence of MetS but also by optimal levels of traditional MetS markers. This suggests that the onset of metabolic disease may begin to manifest well before the primary components of MetS—namely, obesity, hypertension, dyslipidemia, and insulin resistance—become evident. Consequently, early diagnosis and management are essential for preventing or at least delaying the progression of MetS. One proposed method for the early detection of MetS involves measuring expired gases during submaximal exercise at low to moderate intensities [3-5].
Metabolic flexibility
Recent studies have identified mitochondrial dysfunction is a critical factor in the early development of MetS [6], and it is associated with various metabolic disorders, including type 2 diabetes and insulin resistance [7, 8]. The mitochondria’s primary role is to utilize nutrients to generate energy for cellular activities through the process of cellular respiration. Although the bioenergetics of cellular respiration are intricate, the mitochondria’s ability to alternate between energy substrates, primarily fats and carbohydrates (CHO), to produce ATP and fulfill metabolic demands is termed metabolic flexibility (MF) [3]. Impaired MF has recently been recognized as the fundamental cause of mitochondrial dysfunction and, consequently, a significant contributor to numerous contemporary metabolic diseases [3]. Currently, there is no standardized method for assessing mitochondrial function and MF. Existing methods include evaluating oxidative enzymes from muscle biopsies and/or employing cell cultures, both of which are invasive and impractical for the general population [8]. Non-invasive techniques involve the use of nuclear magnetic resonance and magnetic resonance spectroscopy; however, this technology is expensive and not feasible for routine application [7, 8]. Alternative methods encompass glucose and insulin infusions, dietary challenges, epinephrine infusions, sleep challenges, and more recently, sub-maximal exercise [9-12]. Exercise presents an optimal challenge to the metabolic environment of skeletal muscle, where the utilization of fat and CHO within the mitochondria varies according to the stress or exercise intensity imposed on the body [7].
