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Adipose tissue (AT), once considered a mere fat storage organ, is now recognized as a dynamic and complex entity crucial for regulating human physiology, including metabolic processes, energy balance, and immune responses. It comprises mainly two types: white adipose tissue (WAT) for energy storage and brown adipose tissue (BAT) for thermogenesis, with beige adipocytes demonstrating the plasticity of these cells. WAT, beyond lipid storage, is involved in various metabolic activities, notably lipogenesis and lipolysis, critical for maintaining energy homeostasis. It also functions as an endocrine organ, secreting adipokines that influence metabolic, inflammatory, and immune processes. However, dysfunction in WAT, especially related to obesity, leads to metabolic disturbances, including the inability to properly store excess lipids, resulting in ectopic fat deposition in organs like the liver, contributing to non-alcoholic fatty liver disease (NAFLD). This narrative review delves into the multifaceted roles of WAT, its composition, metabolic functions, and the pathophysiology of WAT dysfunction. It also explores diagnostic approaches for adipose-related disorders, emphasizing the importance of accurately assessing AT distribution and understanding the complex relationships between fat compartments and metabolic health. Furthermore, it discusses various therapeutic strategies, including innovative therapeutics like adipose-derived mesenchymal stem cells (ADMSCs)-based treatments and gene therapy, highlighting the potential of precision medicine in targeting obesity and its associated complications. [ABSTRACT FROM AUTHOR]

Background: The assessment of obesity-related health risks has traditionally relied on the Body Mass Index and waist circumference, but their limitations have propelled the need for a more comprehensive approach. The differentiation between visceral (VIS) and subcutaneous (SC) fat provides a finer-grained understanding of these risks, yet practical assessment methods are lacking. We hypothesized that combining the SC-VIS fat ratio with non-invasive biomarkers could create a valuable tool for obesity-related risk assessment. Methods and results: A clinical study of 125 individuals with obesity revealed significant differences in abdominal fat distribution measured by CT-scan among genders and distinct models of obesity, including visceral, subcutaneous, and the SC/VIS ratio. Stratification based on these models highlighted various metabolic changes. The SC/VIS ratio emerged as an excellent metric to differentiate metabolic status. Gene expression analysis identified candidate biomarkers, with ISM1 showing promise. Subsequent validation demonstrated a correlation between ISM1 levels in SC and plasma, reinforcing its potential as a non-invasive biomarker for fat distribution. Serum adipokine levels also correlated with the SC/VIS ratio. The Receiver Operating Characteristic analysis revealed ISM1's efficacy in discriminating individuals with favorable metabolic profiles based on adipose tissue distribution. Correlation analysis also suggested that ISM1 was involved in glucose regulation pathways. Conclusion: The study's results support the hypothesis that the SC-VIS fat ratio and its derived non-invasive biomarkers can comprehensively assess obesity-related health risks. ISM1 could predict abdominal fat partitioning and be a potential biomarker for evaluating obesity-related health risks. [ABSTRACT FROM AUTHOR]

Obesity is a highly prevalent condition often associated with dysfunctional adipose tissue. Stem cell-based therapies have become a promising tool for therapeutic intervention in the context of regenerative medicine. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are the most easily obtained, have immunomodulatory properties, show great ex vivo expansion capacity and differentiation to other cell types, and release a wide variety of angiogenic factors and bioactive molecules, such as growth factors and adipokines. However, despite the positive results obtained in some pre-clinical studies, the actual clinical efficacy of ADMSCs still remains controversial. Transplanted ADMSCs present a meager rate of survival and proliferation, possibly because of the damaged microenvironment of the affected tissues. Therefore, there is a need for novel approaches to generate more functional ADMSCs with enhanced therapeutic potential. In this context, genetic manipulation has emerged as a promising strategy. In the current review, we aim to summarize several adipose-focused treatments of obesity, including cell therapy and gene therapy. Particular emphasis will be given to the continuum from obesity to metabolic syndrome, diabetes, and underlying non-alcoholic fatty liver disease (NAFLD). Furthermore, we will provide insights into the potential shared adipocentric mechanisms involved in these pathophysiological processes and their remediation using ADMSCs. [ABSTRACT FROM AUTHOR]

Objective: Adipose tissue stores a substantial amount of body cholesterol in humans. Obesity is associated with decreased concentrations of serum cholesterol. During weight gain, adipose tissue dysfunction might be one of the causes of metabolic syndrome. The aim of this study is to evaluate cholesterol storage and oxidized metabolites in adipose tissue and their relationship with metabolic clinical characteristics. Methods: Concentrations of cholesterol and oxysterols (27-hydroxycholesterol and 24S-hydroxycholesterol) in subcutaneous and visceral adipose tissue were determined by high-performance liquid chromatography with tandem mass spectrometry in 19 adult women with body mass index between 23 and 40 kg/m2 from the FAT expandability (FATe) study. Tissue concentration values were correlated with biochemical and clinical characteristics using nonparametric statistics. Results: Insulin correlated directly with 24S-hydroxycholesterol in both adipose tissues and with 27-hydroxycholesterol in visceral tissue. Leptin correlated directly with 24S-hydroxycholesterol in subcutaneous adipose tissue. Tissue cholesterol correlated directly with 27-hydroxycholesterol in both adipose tissues and with 24S-hydroxycholesterol in visceral tissue, where cholesterol correlation with 24S-hydroxycholesterol was higher than with 27-hydroxycholesterol. In addition, some tendencies were observed: serum high-density lipoprotein cholesterol tended to be inversely correlated with visceral adipose tissue cholesterol; high-sensitivity C-reactive protein tended to be correlated directly with subcutaneous adipose 24S-hydroxycholesterol and inversely with visceral 27-hydroxycholesterol. Conclusions: Adipose tissue oxysterols are associated with blood insulin and insulin resistance. Tissue cholesterol correlated more with 27-hydroxycholesterol in subcutaneous adipose tissue and with 24S-hydroxycholesterol in visceral adipose tissue. Levels of adipose 24S-hydroxycholesterol seem to be correlated with some metabolic syndrome symptoms and inflammation while adipose 27-hydroxycholesterol could represent some protection against them. [ABSTRACT FROM AUTHOR]

Background: Obesity is an excessive accumulation of fat frequently, but not always, associated with health problems, mainly type 2 diabetes and cardiovascular disease. During a positive energy balance, as caused by excessive intake or sedentary lifestyle, subcutaneous adipose tissue expands and accumulates lipids as triglycerides. However, the amount of adipose tissue per se is unlikely to be the factor linking obesity and metabolic complications. The expandability hypothesis states that, if this positive energy balance is prolonged, a point is eventually reached where subcutaneous adipose tissue can not further expand and energy surplus no longer can be safely stored. Once the limit on storage capacity has been exceeded, the dietary lipids start spilling and accumulate ectopically in other organs (omentum, liver, muscle, pancreas) forming lipid byproducts toxic to cells. Methods/Design: FATe is a multidisciplinary clinical project aimed to fill gaps that still exist in the expandability hypothesis. Imaging techniques (CT-scan), metabolomics, and transcriptomics will be used to identify the factors that set the limit expansion of subcutaneous adipose tissue in a cohort of caucasian individuals with varying degrees of adiposity. Subsequently, a set of biomarkers that inform the individual limits of expandability will be developed using computational and mathematical modeling. A different validation cohort will be used to minimize the risk of false positive rates and increase biomarkers' predictive performance. Discussion: The work proposed here will render a clinically useful screening method to predict which obese individuals will develop metabolic derangements, specially diabetes and cardiovascular disease. This study will also provide mechanistic evidence that promoting subcutaneous fat expansion might be a suitable therapy to reduce metabolic complications associated with positive energy balance characteristic of Westernized societies. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (ε2 , ε3 , and ε4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with demonstrated roles across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes. [ABSTRACT FROM AUTHOR]