What is adipose tissue dysfunction?
Adipose tissue dysfunction not only possesses an important role in the storage of excess nutrients but also acts as a critical immune and endocrine organ. Researchers and clinicians now consider adipose tissue dysfunction to be an active endocrine organ that secretes a variety of humoral factors called “adipokines” that produce significant systemic metabolic effects from food intake to glucose tolerance.
In addition to the production of specific adipokines, Adipose tissue dysfunction also secretes pro-inflammatory cytokines, which contribute to low-grade systemic inflammation, which has become a hallmark of various chronic pathologies associated with metabolic syndromes, such as metastasis and cachexia due to Cancer. These systemic effects are mediated by communication networks derived from a wide variety of resident fat cells, including adipose cells, endothelial cells, neural cells, stem cells, and other precursors, and recent studies have shown that the population of a wide variety of immune cells plays a key role in the development of adipose tissue and abnormalities.
In this chapter, we describe the various molecular ways in which excessive fat lipid storage is associated with chronic inflammation and review current knowledge on the triggers of esophagus and coccyx-related inflammation in adipose tissue. Finally, we describe how interference between adipose tissue inflammation and non-resident adipocyte cells in tissues is involved in this metabolic alteration.
Disturbed adipose tissue (AT) dysfunction function in PCOS
Adipose tissue dysfunction is regarded as an endocrine organ that plays a major role in the regulation of glucose and lipid metabolism and storage, with an impact on energy expenditure, inflammation and immunity, cardiovascular function, and reproduction, among other functions. Adipocytes are the major, but not the sole constituent of adipose tissue, which also contains fibroblasts, macrophages, stromal cells, monocytes (MNCs), and preadipocytes, and is a rich source of stem cells. Adipogenesis develops as a two-step process: undifferentiated mesenchymal cells convert into preadipocytes, which then differentiate to lipid-filled adipocytes.
The location and distribution of adipose tissue are function related. In general, subcutaneous (SC) adipose tissue has been associated with temperature regulation and with specific female and male fat distribution patterns. In turn, visceral or omental (OM) adipose tissue is responsible for maintaining organs in the normal position, occupying the spaces between them. Greater SC and mainly ON mass and adipocyte size have been linked to hepatic and peripheral insulin resistance as well as metabolic comorbidities such as dyslipidemia, decreased glucose tolerance, diabetes, and hypertension.
In addition, under metabolic stress, adipose tissue dysfunction expansion is altered, causing hypertrophy rather than hyperplasia. Adipose hypertrophy is associated with a lower number of adipocytes than adipose hyperplasia. In fact, the pathophysiological mechanism of fat expansion in hyperplasia is less deleterious, being the adipocytes still functional. In turn, hypertrophic adipocytes are more susceptible to inflammation, apoptosis, fibrosis, and release of free fatty acids.
Moreover, OM adipose tissue in women with PCOS may present specific functional derangements, related to increased catecholamine-induced lipolysis and possibly linked to altered stoichiometric properties of the adipose protein kinase hormone-sensitive lipase.
PCOS is closely linked to functional derangements in adipose tissue dysfunction, although the mechanisms underlying this association are not well established. As described for metabolic stress, adipocytes seem to be prone to hypertrophy when exposed to androgen excess, as experienced by PCOS women, and both adipose tissue hypertrophy and hyperandrogenism are related to insulin resistance. Moreover, evidence suggests that reduced catecholamine-induced lipolysis in SC adipocytes may also be associated with adipocyte hypertrophy in PCOS.
Oxygen tension of adipose tissue (AT) dysfunction in human balance
Since adipose tissue dysfunction has been identified as an important process in the pathophysiology of esophageal disorders, the number of studies aimed at identifying the trigger for adipose tissue dysfunction has increased significantly. The prevailing notion is that insufficient oxygen in adipose tissue is commonly called “adipose tissue hypoxia,” which refers to adipose tissue dysfunction in obesity.
It has been proposed that adipose tissue angiogenesis is inadequate to maintain normoxia in adipose tissue during the progressive development of obsolescence. In other words, reduced oxygen delivery to tissue is proposed to induce adipose tissue dysfunction. It is true that angiogenic genes (eg, VEGF) and lower capillary density were found in abdominal subcutaneous adipose tissue compared to lean individuals. The net result of the structural and functional properties of the adipose tissue vasculature determines tissue blood flow.
A consistent observation made by our lab and others is that fasting and postprandial ATBF decreases in lean insulin-resistant or insulin-sensitive versus insulin-sensitive subjects, indicating that the oxygen supply to adipose tissue is actually weaker. We recently demonstrated for the first time that both ATBF drug (local administration of vasoactive agents) and ATBF physiological manipulation (oral glucose drink) induce similar changes in adipose tissue oxygen partial pressure (AT PO2) in humans. ), Which indicates that the supply of oxygen to adipose tissue actually affects AT PO2.
The second argument proposed to develop the concept of hypoxia of adipose tissue in ob arrhythmia is that the diameter of hypertrophic adipocytes in arrhythmia exceeds the normal diffusion distance of oxygen in the tissues (100-200 m). However, in human adipose tissue, there appears to be only a very small proportion of fat cells with a diameter> 100 µm. Therefore, the importance of reducing oxygen diffusion from capillaries to hypertrophic fat cells in obese humans can be questioned.
Conclusion and future directions
Adipose tissue dysfunction is a key factor in the pathophysiology of chronic cardiovascular and metabolic diseases. Recent studies have suggested that changes in AT PO2 can cause adipose tissue dysfunction in obese patients, although many questions remain. More research is needed on the functional effects of AT PO2, as well as modified AT PO2, in well-characterized observational and clinical intervention studies in humans.
Important factors to consider in future studies are the severity, duration, and pattern of exposure to PO2, as different experimental conditions may indicate different study results. In addition, it is of particular interest to examine the differences in fat stores in AT PO2 (eg, lower body versus upper body) and to discover whether metabolic and inflammatory responses to chronic physiological levels of O2 are related to fat deposits and specific cell types. [For example, adipocyte (anterior), vascular stromal cells, macrophages] and/or donor characteristics.
Furthermore, it is important to understand whether AT PO2 is more strongly related to metabolic syndrome (eg, insulin resistance) in obesity than to increased adipose tissue mass. Finally, human intervention studies are needed to determine if AT can modify PO2 (eg, weight loss, oxygen therapy) and subsequently cause changes in metabolism and inflammatory phenotype. These studies should be comprehensive in nature combined with measurements in tissue biopsies and cell culture experiments, in vivo evaluation of adipose tissue, and whole-body physiology.
Studies in this exciting field of research may lead to new opportunities for therapeutic intervention in obese people with adipose tissue dysfunction, thereby improving cardiometabolic health.