The Project ATA: Adipose Tissue & Adipokines

Overview

It is essential to delve deeper into the molecular and tissue aspects that allow us to recognize the roles of adipose tissue and its interaction with the musculoskeletal (i.e., adipomyokines) to facilitate the identification of biomarkers that can complement the assessment of body composition. Thus, investigators posed the following research question: what characteristics of adipose tissue can investigators consider to rethink assessment for the diagnosis and treatment of obesity? The 'Project ATA' is a cross-sectional study based on the Strengthening the Reporting of Observational Studies in Epidemiology-Nutritional Epidemiology (STROBE-nut) guidelines, an Extension of the STROBE Statement. The FINER strategy (Feasible, Interesting, Novel, Ethical, and Relevant) and previously published guidelines for organizing a multicenter study will be followed. The 'Project ATA' will test the associations of several morphological metrics and adipomyokines in order to both profile populations with excess body fat and to establish practical geographical-based recommendations for practitioners.

Obesity is a multifactorial disease characterized by excess and accumulation of body fat, which implies hypertrophy and hyperplasia of adipocytes (i.e. adipose tissue cells). However, obesity is not only related to lipid accumulation in adipose tissue but could also generate morpho-functional changes in other tissues. The deleterious effects of lipid accumulation in non-adipose tissues are known as lipotoxicity. Lipotoxicity generates certain metabolic alterations, which affect overall metabolic health, leading to ectopic fat accumulation (i.e. fat accumulation outside its proper place). These factors can result in an increased likelihood of chronic diseases, including cardiovascular disease, type 2 diabetes mellitus, non-alcoholic fatty liver disease, chronic kidney disease, and different types of cancer. There is substantial variation between individuals, some obese people may remain metabolically healthy and some lean people may have metabolic diseases. Additionally, adipose tissue in addition to having an energy storage role produces hormones that regulate different physiological processes, such as inflammatory responses, mechanical cushioning and insulation, and participation in heat production for body temperature regulation. These processes can change adaptively (or maladaptation) during the loss or gain of body mass. Importantly, insufficient adipose tissue (lipodystrophy) or adipose tissue dysfunction (e.g. obesity) leads to excessive lipid deposition in other organs such as the liver and muscle. Obesity comprises much damage in different tissues of the organism; however, these changes are potentially reversible by taking advantage of the innate property of biological systems to favor adaptation to repeated stimuli (e.g., changes in habits and lifestyles). The particularity of obesity is the expansion of adipose tissue, although this does not always mean that it is pathological. A clear example is natural obesity in various mammals during the pre-hibernation stage and subsequent periods of high physical activity. Healthy adipose tissue expansion is accompanied by adequate capillary angiogenesis and mitochondria-centered metabolic control. On the other hand, unhealthy adipose tissue expansion is associated with capillary and mitochondrial impairment, resulting in immune cell deposition and excessive production of proinflammatory cytokines. In addition, some pathologies of metabolically healthy obese individuals have well-preserved adipose tissue function, associated with fewer comorbidities and lower mortality rates compared to lean individuals. The reasons for studying beyond the energetic function of adipose tissue are based on the plasticity of adipose tissue and its different types (both morphological and metabolic). Traditionally, adipose tissue is classified as white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue (bAT). However, other types of adipose tissue have been identified, including pink and yellow (bone marrow) adipose tissue, highlighting their physiological functions after trans-differentiation processes. It is necessary to establish an understanding of the complexity of adipose tissue and its endocrine interaction with other tissues to determine the physiological response to external stimuli (e.g., overenergetic diet, physical inactivity, sedentary lifestyle, cancer, etc.). In fact, a geographical variation of obesity and the associated risk factors has been reported by different research groups. This questions and highlights the need to improve the obesity metrics for diagnosis and monitoring. The aim of 'Project ATA' is double: i) to profile the population with excess fat mass (overweight and obesity) using body composition data and the concentration of adipomyokines, and ii) to evaluate the association between morphophysiological and endocrine variables in order to propose practical geographical-based recommendations to assess and monitor obesity accurately.