About this Research Topic
Obesity is a worldwide epidemics, that represents a major public health problem, due to its associated risk for type 2 diabetes, metabolic syndrome, cardiovascular diseases, and some types of cancers. The rising prevalence of obesity and its comorbidities has therefore promoted more interest in studies on the physiological role of adipose tissue - previously considered as a simple, inert reservoir of lipids.
In the last twenty years, many biologically active molecules produced by this tissue have been identified, evoking a role of fat in previously unsuspected processes, including inflammation, insulin response and glucose homeostasis, angiogenesis, and haemostasis. Hormonal factors produced by adipose cells have been collectively called “adipokines”, and include about a hundred of known molecules, such as leptin, adiponectin, resistin, apelin, visfatin, VEGF, PAI-1, and many other, not yet identified factors that have more recently emerged by proteomic strategies. Later, it has been postulated that the adipose tissue of the obese, becoming dysfunctional by changes in the secretion pattern of adipokines, may sustain inflammation, insulin resistance, and a pro-thrombotic state, associated with endothelial impairment - all conditions underpinning obesity-related comorbidities. Recently, the notion of obesity as a systemic, low-grade inflammatory state, that favours insulin resistance, has become commonly accepted, but the event(s) and the related molecular mechanisms that initially trigger adipose tissue dysfunction in the obese have remained still poorly understood. Among these, a direct role of hypoxia in adipose, and non-adipose cells in the fat tissue, has been hypothesized on the basis of theoretical considerations, and demonstrated in animal models and in vitro studies. Oxidative stress, endoplasmic reticulum (ER) stress, and the activation of the unfolded protein response (UPR) represent additional cellular processes, indirectly linked to hypoxia, that may be operative in hypertrophic fat cells.
Hypoxia-inducible factor 1 (HIF-1) is considered the main transcription factor that mediates the cellular response to low oxygen tension. Although the scenario is far from be complete, many HIF-1-inducible genes have been identified in the adipose tissue, including leptin, VEGF, GLUT1, metalloproteinases MMP2 and MMP9, IL-4, IL-6, and PAI-1, implicating a molecular role of hypoxia in important processes, such as inflammation, metabolism, insulin resistance, and angiogenesis. Also, the molecular interplay between HIF-1 and other nuclear partners, such as NF-kB, HIF-2, CREB, and PPARγ, involved in the gene networks affected by oxygen availability, deserves further investigation. Thus, the aim of this topic is to provide new insights into the molecular mechanisms that are triggered by hypoxia in obesity. A better understanding of the role of hypoxia in the adipose tissue may contribute to deepen our knowledge on the pathophysiology of obesity and related disorders, and may suggest innovative targets for preventive and/or therapeutic strategies.
In the last twenty years, many biologically active molecules produced by this tissue have been identified, evoking a role of fat in previously unsuspected processes, including inflammation, insulin response and glucose homeostasis, angiogenesis, and haemostasis. Hormonal factors produced by adipose cells have been collectively called “adipokines”, and include about a hundred of known molecules, such as leptin, adiponectin, resistin, apelin, visfatin, VEGF, PAI-1, and many other, not yet identified factors that have more recently emerged by proteomic strategies. Later, it has been postulated that the adipose tissue of the obese, becoming dysfunctional by changes in the secretion pattern of adipokines, may sustain inflammation, insulin resistance, and a pro-thrombotic state, associated with endothelial impairment - all conditions underpinning obesity-related comorbidities. Recently, the notion of obesity as a systemic, low-grade inflammatory state, that favours insulin resistance, has become commonly accepted, but the event(s) and the related molecular mechanisms that initially trigger adipose tissue dysfunction in the obese have remained still poorly understood. Among these, a direct role of hypoxia in adipose, and non-adipose cells in the fat tissue, has been hypothesized on the basis of theoretical considerations, and demonstrated in animal models and in vitro studies. Oxidative stress, endoplasmic reticulum (ER) stress, and the activation of the unfolded protein response (UPR) represent additional cellular processes, indirectly linked to hypoxia, that may be operative in hypertrophic fat cells.
Hypoxia-inducible factor 1 (HIF-1) is considered the main transcription factor that mediates the cellular response to low oxygen tension. Although the scenario is far from be complete, many HIF-1-inducible genes have been identified in the adipose tissue, including leptin, VEGF, GLUT1, metalloproteinases MMP2 and MMP9, IL-4, IL-6, and PAI-1, implicating a molecular role of hypoxia in important processes, such as inflammation, metabolism, insulin resistance, and angiogenesis. Also, the molecular interplay between HIF-1 and other nuclear partners, such as NF-kB, HIF-2, CREB, and PPARγ, involved in the gene networks affected by oxygen availability, deserves further investigation. Thus, the aim of this topic is to provide new insights into the molecular mechanisms that are triggered by hypoxia in obesity. A better understanding of the role of hypoxia in the adipose tissue may contribute to deepen our knowledge on the pathophysiology of obesity and related disorders, and may suggest innovative targets for preventive and/or therapeutic strategies.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
