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American Journal of Physiology. Cell... Mar 2021Several lines of preclinical and clinical research have confirmed that chronic low-grade inflammation of adipose tissue is mechanistically linked to metabolic disease... (Review)
Review
Several lines of preclinical and clinical research have confirmed that chronic low-grade inflammation of adipose tissue is mechanistically linked to metabolic disease and organ tissue complications in the overweight and obese organism. Despite this widely confirmed paradigm, numerous open questions and knowledge gaps remain to be investigated. This is mainly due to the intricately intertwined cross-talk of various pro- and anti-inflammatory signaling cascades involved in the immune response of expanding adipose depots, particularly the visceral adipose tissue. Adipose tissue inflammation is initiated and sustained over time by dysfunctional adipocytes that secrete inflammatory adipokines and by infiltration of bone marrow-derived immune cells that signal via production of cytokines and chemokines. Despite its low-grade nature, adipose tissue inflammation negatively impacts remote organ function, a phenomenon that is considered causative of the complications of obesity. The aim of this review is to broadly present an overview of adipose tissue inflammation by highlighting the most recent reports in the scientific literature and summarizing our overall understanding of the field. We also discuss key endogenous anti-inflammatory mediators and analyze their mechanistic role(s) in the pathogenesis and treatment of adipose tissue inflammation. In doing so, we hope to stimulate studies to uncover novel physiological, cellular, and molecular targets for the treatment of obesity.
Topics: Adipocytes; Adipose Tissue; Animals; Cytokines; Humans; Inflammation; Metabolic Diseases; Obesity
PubMed: 33356944
DOI: 10.1152/ajpcell.00379.2020 -
Cell Feb 2022Adipose tissue, colloquially known as "fat," is an extraordinarily flexible and heterogeneous organ. While historically viewed as a passive site for energy storage, we... (Review)
Review
Adipose tissue, colloquially known as "fat," is an extraordinarily flexible and heterogeneous organ. While historically viewed as a passive site for energy storage, we now appreciate that adipose tissue regulates many aspects of whole-body physiology, including food intake, maintenance of energy levels, insulin sensitivity, body temperature, and immune responses. A crucial property of adipose tissue is its high degree of plasticity. Physiologic stimuli induce dramatic alterations in adipose-tissue metabolism, structure, and phenotype to meet the needs of the organism. Limitations to this plasticity cause diminished or aberrant responses to physiologic cues and drive the progression of cardiometabolic disease along with other pathological consequences of obesity.
Topics: Adaptation, Physiological; Adipocytes, White; Adipose Tissue; Animals; Disease; Health; Humans; Thermogenesis
PubMed: 35120662
DOI: 10.1016/j.cell.2021.12.016 -
Circulation Research Apr 2021Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin... (Review)
Review
Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin resistance, which collectively contribute to the development of cardiovascular diseases and resultant morbidity and mortality. Forty-two percent of adults in the United States are obese, and a total of 1.9 billion adults worldwide are overweight or obese. These alarming numbers, which continue to climb, represent a major health and economic burden. Adipose tissue is a highly dynamic organ that can be classified based on the cellular composition of different depots and their distinct anatomical localization. Massive expansion and remodeling of adipose tissue during obesity differentially affects specific adipose tissue depots and significantly contributes to vascular dysfunction and cardiovascular diseases. Visceral adipose tissue accumulation results in increased immune cell infiltration and secretion of vasoconstrictor mediators, whereas expansion of subcutaneous adipose tissue is less harmful. Therefore, fat distribution more than overall body weight is a key determinant of the risk for cardiovascular diseases. Thermogenic brown and beige adipose tissue, in contrast to white adipose tissue, is associated with beneficial effects on the vasculature. The relationship between the type of adipose tissue and its influence on vascular function becomes particularly evident in the context of the heterogenous phenotype of perivascular adipose tissue that is strongly location dependent. In this review, we address the abnormal remodeling of specific adipose tissue depots during obesity and how this critically contributes to the development of hypertension, endothelial dysfunction, and vascular stiffness. We also discuss the local and systemic roles of adipose tissue derived secreted factors and increased systemic inflammation during obesity and highlight their detrimental impact on cardiovascular health.
Topics: Adipose Tissue; Adiposity; Animals; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Heart Disease Risk Factors; Homeostasis; Humans; Hypertension; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Mice; Obesity; Overweight; Subcutaneous Fat; Vascular Diseases; Vascular Stiffness; Vasoconstriction
PubMed: 33793327
DOI: 10.1161/CIRCRESAHA.121.318093 -
Cell Metabolism Mar 2023Adipose tissue exhibits remarkable plasticity with capacity to change in size and cellular composition under physiological and pathophysiological conditions. The... (Review)
Review
Adipose tissue exhibits remarkable plasticity with capacity to change in size and cellular composition under physiological and pathophysiological conditions. The emergence of single-cell transcriptomics has rapidly transformed our understanding of the diverse array of cell types and cell states residing in adipose tissues and has provided insight into how transcriptional changes in individual cell types contribute to tissue plasticity. Here, we present a comprehensive overview of the cellular atlas of adipose tissues focusing on the biological insight gained from single-cell and single-nuclei transcriptomics of murine and human adipose tissues. We also offer our perspective on the exciting opportunities for mapping cellular transitions and crosstalk, which have been made possible by single-cell technologies.
Topics: Humans; Animals; Mice; Adipocytes; Adipogenesis; Adipose Tissue; Gene Expression Profiling; Cell Differentiation
PubMed: 36889280
DOI: 10.1016/j.cmet.2023.02.002 -
Gaceta Medica de Mexico 2020Adipose tissue is an endocrine organ with high metabolic activity. Countless adipose tissue-secreted adipokines and lipokines, as well as peptides and lipids with... (Review)
Review
Adipose tissue is an endocrine organ with high metabolic activity. Countless adipose tissue-secreted adipokines and lipokines, as well as peptides and lipids with biological activity have thus far been discovered. Both white and brown and beige adipose tissue are known to contribute to energy homeostasis and metabolic regulation. The purpose of this review is to report on the most recent findings related to adipose tissue according to its color and its relationship with metabolic alterations associated with obesity. After a review of the specialized literature, white, brown and beige adipocyte populations were identified to be able to coexist within the same structure, and to modify global metabolic state in physiological or pathological situations.
Topics: Adipose Tissue, Beige; Adipose Tissue, Brown; Adipose Tissue, White; Color
PubMed: 32285854
DOI: 10.24875/GMM.M20000356 -
Endocrine Reviews Jan 2020Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central... (Review)
Review
Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute activation increases metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and includes secretion of factors, known as batokines, which target several different cell types within BAT, and promote adipogenesis, angiogenesis, immune cell interactions, and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies have also provided exciting data on whole body metabolic regulation with a broad spectrum of mechanisms involving BAT crosstalk with liver, skeletal muscle, and gut as well as the central nervous system. These widespread interactions might reflect the property of BAT of switching between an active thermogenic state where energy is highly consumed and drained from the circulation, and the passive thermoneutral state, where energy consumption is turned off. (Endocrine Reviews 41: XXX - XXX, 2020).
Topics: Adipogenesis; Adipose Tissue, Brown; Adipose Tissue, White; Adult; Animals; Cell Plasticity; Energy Metabolism; Humans; Infant; Muscle, Skeletal
PubMed: 31638161
DOI: 10.1210/endrev/bnz007 -
Adipocyte Dec 2021Mammalian adipose tissue can be divided into two major types, namely, white adipose tissue (WAT) and brown adipose tissue (BAT). According to classical view, the main... (Review)
Review
Mammalian adipose tissue can be divided into two major types, namely, white adipose tissue (WAT) and brown adipose tissue (BAT). According to classical view, the main function of WAT is to store excess energy in the form of triglycerides, while BAT is a thermogenic tissue that acts a pivotal part in maintaining the core body temperature. White adipocytes display high plasticity and can transdifferentiate into beige adipocytes which have many similar morphological and functional properties with brown adipocytes under the stimulations of exercise, cold exposure and other factors. This phenomenon is also known as 'browning of WAT'. In addition to transdifferentiation, beige adipocytes can also come from de novo differentiation from tissue-resident progenitors. Activating BAT and inducing browning of WAT can accelerate the intake of glycolipids and reduce the insulin secretion requirement, which may be a new strategy to improve glycolipids metabolism and insulin resistance of obese and type 2 diabetes mellitus (T2DM) patients. This review mainly discusses the significance of brown and beige adipose tissues in the treatment of obesity and T2DM, and focuses on the effect of the browning agent on obesity and T2DM, which provides a brand-new theoretical reference for the prevention and treatment of obesity and T2DM.
Topics: Adipocytes, Beige; Adipocytes, Brown; Adipocytes, White; Adipose Tissue; Adipose Tissue, Beige; Adipose Tissue, Brown; Adipose Tissue, White; Cell Transdifferentiation; Diabetes Mellitus, Type 2; Energy Metabolism; Humans; Insulin Resistance; Obesity; Thermogenesis
PubMed: 33403891
DOI: 10.1080/21623945.2020.1870060 -
Circulation Research Jan 2021The landmark discoveries of leptin and adiponectin firmly established adipose tissue as a sophisticated and highly active endocrine organ, opening a new era of... (Review)
Review
The landmark discoveries of leptin and adiponectin firmly established adipose tissue as a sophisticated and highly active endocrine organ, opening a new era of investigating adipose-mediated tissue crosstalk. Both obesity-associated hyperleptinemia and hypoadiponectinemia are important biomarkers to predict cardiovascular outcomes, suggesting a crucial role for adiponectin and leptin in obesity-associated cardiovascular disorders. Normal physiological levels of adiponectin and leptin are indeed essential to maintain proper cardiovascular function. Insufficient adiponectin and leptin signaling results in cardiovascular dysfunction. However, a paradox of high levels of both leptin and adiponectin is emerging in the pathogenesis of cardiovascular disorders. Here, we (1) summarize the recent progress in the field of adiponectin and leptin and its association with cardiovascular disorders, (2) further discuss the underlying mechanisms for this new paradox of leptin and adiponectin action, and (3) explore the possible application of partial leptin reduction, in addition to increasing the adiponectin/leptin ratio as a means to prevent or reverse cardiovascular disorders.
Topics: Adiponectin; Adipose Tissue; Animals; Anti-Obesity Agents; Bariatric Surgery; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Humans; Leptin; Metabolism, Inborn Errors; Obesity; Signal Transduction
PubMed: 33411633
DOI: 10.1161/CIRCRESAHA.120.314458 -
The Journal of Clinical Investigation Oct 2019Obesity originates from an imbalance between caloric intake and energy expenditure that promotes adipose tissue expansion, which is necessary to buffer nutrient excess.... (Review)
Review
Obesity originates from an imbalance between caloric intake and energy expenditure that promotes adipose tissue expansion, which is necessary to buffer nutrient excess. Patients with higher visceral fat mass are at a higher risk of developing severe complications such as type 2 diabetes and cardiovascular and liver diseases. However, increased fat mass does not fully explain obesity's propensity to promote metabolic diseases. With chronic obesity, adipose tissue undergoes major remodeling, which can ultimately result in unresolved chronic inflammation leading to fibrosis accumulation. These features drive local tissue damage and initiate and/or maintain multiorgan dysfunction. Here, we review the current understanding of adipose tissue remodeling with a focus on obesity-induced adipose tissue fibrosis and its relevance to clinical manifestations.
Topics: Adipocytes; Adipose Tissue; Animals; Fibrosis; Humans; Inflammation; Metabolic Diseases; Mice; Myofibroblasts; Neovascularization, Physiologic; Obesity; Stem Cells
PubMed: 31498150
DOI: 10.1172/JCI129192 -
Cells Dec 2021The long-held belief about adipose tissue was that it was relatively inert in terms of biological activity. It was believed that its primary role was energy storage;...
The long-held belief about adipose tissue was that it was relatively inert in terms of biological activity. It was believed that its primary role was energy storage; however, that was shattered with the discovery of adipokines. Scientists interested in regenerative medicine then reported that adipose tissue is rich in adult stromal/stem cells. Following these initial reports, adipose stem cells (ASCs) rapidly garnered interest for use as potential cellular therapies. The primary advantages of ASCs compared to other mesenchymal stem cells (MSCs) include the abundance of the tissue source for isolation, the ease of methodologies for tissue collection and cell isolation, and their therapeutic potential. Studies conducted both in vitro and in vivo have demonstrated that ASCs are multipotent, possessing the ability to differentiate into cells of mesodermal origins, including adipocytes, chondrocytes, osteoblast and others. Moreover, ASCs produce a broad array of cytokines, growth factors, nucleic acids (miRNAs), and other macromolecules into the surrounding milieu by secretion or in the context of microvesicles. The secretome of ASCs has been shown to alter tissue biology, stimulate tissue-resident stem cells, change immune cell activity, and mediate therapeutic outcomes. The quality of ASCs is subject to donor-to-donor variation driven by age, body mass index, disease status and possibly gender and ethnicity. This review discusses adipose stromal/stem cell action mechanisms and their potential utility as cellular therapeutics.
Topics: Adipocytes; Adipose Tissue; Cell Differentiation; Chondrocytes; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Secretome
PubMed: 34943941
DOI: 10.3390/cells10123433