The overall prevalence of obesity increased dramatically over the last few decades [1–3]. The World Health Organization (WHO) reported that more than 1.9 billion adults around the world are overweight, and nearly one-third of the population is obese [4].

From an epidemiological perspective, obesity is linked to so-called non-communicable diseases (NCDs), a set of diseases of long duration and slow progression, including cardiovascular diseases, diabetes mellitus type 2, respiratory diseases, and certain types of cancer [5]. These NCDs kill 41 million people each year, equivalent to 71% of all deaths globally [6]; 1.6 million deaths annually can be attributed to insufficient physical activity [7].

In general, obesity is still defined on the basis of body mass index (BMI), and BMI in itself is generally accepted as a strong predictor of overall early mortality [3]. The increased health risk is particularly linked to high amounts of white and/or visceral fat because of its endocrine activities. Visceral adipose tissue produces more than 600 so-called adipokines that regulate not only metabolic processes such as insulin secretion, hunger and satiety, and energy balance, but inflammatory processes as well [8]. An increasing accumulation of visceral fat in terms of chronic overfeeding results in dysfunctional adipose tissue with excessive adipokine secretion and an altered secretion profile characterized by increased leptin, interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels, as well as increased oxidative stress and a reduction in adiponectin [9], leading to chronic low-grade inflammation.

Whereas physical activity/exercise can be protective against these pathological conditions [10], physical inactivity enhances the inflammatory mechanisms described above [11]. This might be explained by the specific function of skeletal muscle mass. Skeletal muscle is the largest organ in the body; its energy production and consumption are fundamental to metabolic control. Currently, skeletal muscle is also identified as an endocrine organ secreting hundreds of so-called myokines such as myostatin, IL-4, IL-6, IL-7, IL-15, myonectin, follistatin-like 1 (FSTL1), leukemia inhibitory factor, and/or irisin [12,13]. Not only do these myokines act locally in the muscle in an autocrine/paracrine manner, but they are also released into the bloodstream as endocrine factors to regulate physiological processes in other tissues. The release of myokines from contracting muscle is assumed to be at least partly responsible for the health-promoting effects of physical activity that protects against major chronic, low-grade inflammatory diseases like type 2 diabetes, insulin resistance, metabolic syndrome, and many others.

In 2013, Raschke and Eckel [14] described the interplay between muscle and adipose tissue as a two-edged sword. They pointed out that certain cytokines are released by both skeletal muscle and adipose tissue, exhibiting a bioactive effect. The authors suggested calling them adipo-myokines because they are both mediators of exercise and mediators of inflammation. For this reason, as well as for the development of tailored prevention and treatment, it is important to better understand the molecular mechanisms and potential influencing factors that predispose obese (or inactive) individuals to the development of metabolic diseases. Increasing evidence also suggests that early-life exposure to a range of environmental factors, including parental BMI and lifestyle (e.g., maternal nutrition), plays a critical role in defining an offspring’s metabolic health. According to the Developmental Origins of Health and Disease hypothesis, environmental exposures during critical periods—such as the preconception, fetal, and early infant phases of life—can influence development and have a persistent impact on metabolic health and gene expression, thereby influencing offspring phenotype and disease risk in later life (Figure 1) [15,16].

The particular aim of this article is to explore the extent to which biomolecular findings can substantiate the concept of metabolic health and to investigate the role of physical activity/exercise, using cardiorespiratory fitness as a surrogate marker considering early-life factors.

Figure 1. Illustration of the interaction of parental factors on offspring in pregnancy, affecting epigenetic regulation and different organ systems in the development of different obesity phenotypes in terms of metabolic health.

The publication can be found here: https://www.mdpi.com/1422-0067/20/24/6159/htm