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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 Jan 2018Adipose tissue depots can exist in close association with other organs, where they assume diverse, often non-traditional functions. In stem cell-rich skin, bone marrow,... (Review)
Review
Adipose tissue depots can exist in close association with other organs, where they assume diverse, often non-traditional functions. In stem cell-rich skin, bone marrow, and mammary glands, adipocytes signal to and modulate organ regeneration and remodeling. Skin adipocytes and their progenitors signal to hair follicles, promoting epithelial stem cell quiescence and activation, respectively. Hair follicles signal back to adipocyte progenitors, inducing their expansion and regeneration, as in skin scars. In mammary glands and heart, adipocytes supply lipids to neighboring cells for nutritional and metabolic functions, respectively. Adipose depots adjacent to skeletal structures function to absorb mechanical shock. Adipose tissue near the surface of skin and intestine senses and responds to bacterial invasion, contributing to the body's innate immune barrier. As the recognition of diverse adipose depot functions increases, novel therapeutic approaches centered on tissue-specific adipocytes are likely to emerge for a range of cancers and regenerative, infectious, and autoimmune disorders.
Topics: Adipose Tissue; Animals; Humans; Models, Biological; Organ Specificity
PubMed: 29320711
DOI: 10.1016/j.cmet.2017.12.002 -
International Journal of Molecular... May 2019Obesity is a critical risk factor for the development of type 2 diabetes (T2D), and its prevalence is rising worldwide. White adipose tissue (WAT) has a crucial role in... (Review)
Review
Obesity is a critical risk factor for the development of type 2 diabetes (T2D), and its prevalence is rising worldwide. White adipose tissue (WAT) has a crucial role in regulating systemic energy homeostasis. Adipose tissue expands by a combination of an increase in adipocyte size (hypertrophy) and number (hyperplasia). The recruitment and differentiation of adipose precursor cells in the subcutaneous adipose tissue (SAT), rather than merely inflating the cells, would be protective from the obesity-associated metabolic complications. In metabolically unhealthy obesity, the storage capacity of SAT, the largest WAT depot, is limited, and further caloric overload leads to the fat accumulation in ectopic tissues (e.g., liver, skeletal muscle, and heart) and in the visceral adipose depots, an event commonly defined as "lipotoxicity." Excessive ectopic lipid accumulation leads to local inflammation and insulin resistance (IR). Indeed, overnutrition triggers uncontrolled inflammatory responses in WAT, leading to chronic low-grade inflammation, therefore fostering the progression of IR. This review summarizes the current knowledge on WAT dysfunction in obesity and its associated metabolic abnormalities, such as IR. A better understanding of the mechanisms regulating adipose tissue expansion in obesity is required for the development of future therapeutic approaches in obesity-associated metabolic complications.
Topics: Adipogenesis; Adipose Tissue; Animals; Diabetes Mellitus, Type 2; Humans; Inflammation; Insulin Resistance; Obesity; Subcutaneous Fat
PubMed: 31085992
DOI: 10.3390/ijms20092358 -
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 -
Nature Metabolism Feb 2019Adipose tissue possesses the remarkable capacity to control its size and function in response to a variety of internal and external cues, such as nutritional status and... (Review)
Review
Adipose tissue possesses the remarkable capacity to control its size and function in response to a variety of internal and external cues, such as nutritional status and temperature. The regulatory circuits of fuel storage and oxidation in white adipocytes and thermogenic adipocytes (brown and beige adipocytes) play a central role in systemic energy homeostasis, whereas dysregulation of the pathways is closely associated with metabolic disorders and adipose tissue malfunction, including obesity, insulin resistance, chronic inflammation, mitochondrial dysfunction, and fibrosis. Recent studies have uncovered new regulatory elements that control the above parameters and provide new mechanistic opportunities to reprogram fat cell fate and function. In this Review, we provide an overview of the current understanding of adipocyte metabolism in physiology and disease and also discuss possible strategies to alter fuel utilization in fat cells to improve metabolic health.
Topics: Adaptation, Physiological; Adipocytes, Beige; Adipose Tissue; Animals; Cellular Reprogramming; Energy Metabolism; Humans; Lipolysis; Mitochondria; Thermogenesis
PubMed: 31903450
DOI: 10.1038/s42255-018-0021-8 -
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 -
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 -
American Journal of Physiology. Cell... May 2021Adipocytes are specialized cells with pleiotropic roles in physiology and pathology. Several types of fat cells with distinct metabolic properties coexist in various... (Review)
Review
Adipocytes are specialized cells with pleiotropic roles in physiology and pathology. Several types of fat cells with distinct metabolic properties coexist in various anatomically defined fat depots in mammals. White, beige, and brown adipocytes differ in their handling of lipids and thermogenic capacity, promoting differences in size and morphology. Moreover, adipocytes release lipids and proteins with paracrine and endocrine functions. The intrinsic properties of adipocytes pose specific challenges in culture. Mature adipocytes float in suspension culture due to high triacylglycerol content and are fragile. Moreover, a fully differentiated state, notably acquirement of the unilocular lipid droplet of white adipocyte, has so far not been reached in two-dimensional culture. Cultures of mouse and human-differentiated preadipocyte cell lines and primary cells have been established to mimic white, beige, and brown adipocytes. Here, we survey various models of differentiated preadipocyte cells and primary mature adipocyte survival describing main characteristics, culture conditions, advantages, and limitations. An important development is the advent of three-dimensional culture, notably of adipose spheroids that recapitulate in vivo adipocyte function and morphology in fat depots. Challenges for the future include isolation and culture of adipose-derived stem cells from different anatomic location in animal models and humans differing in sex, age, fat mass, and pathophysiological conditions. Further understanding of fat cell physiology and dysfunction will be achieved through genetic manipulation, notably CRISPR-mediated gene editing. Capturing adipocyte heterogeneity at the single-cell level within a single fat depot will be key to understanding diversities in cardiometabolic parameters among lean and obese individuals.
Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Cell Communication; Cell Culture Techniques; Cell Line; Cell Survival; Humans; Phenotype; Species Specificity; Spheroids, Cellular; Tissue Culture Techniques
PubMed: 33439778
DOI: 10.1152/ajpcell.00519.2020 -
Trends in Cell Biology Apr 2022The important role of mitochondria in the regulation of white adipose tissue (WAT) remodeling and energy balance is increasingly appreciated. The remarkable... (Review)
Review
The important role of mitochondria in the regulation of white adipose tissue (WAT) remodeling and energy balance is increasingly appreciated. The remarkable heterogeneity of the adipose tissue stroma provides a cellular basis to enable adipose tissue plasticity in response to various metabolic stimuli. Regulating mitochondrial function at the cellular level in adipocytes, in adipose progenitor cells (APCs), and in adipose tissue macrophages (ATMs) has a profound impact on adipose homeostasis. Moreover, mitochondria facilitate the cell-to-cell communication within WAT, as well as the crosstalk with other organs, such as the liver, the heart, and the pancreas. A better understanding of mitochondrial regulation in the diverse adipose tissue cell types allows us to develop more specific and efficient approaches to improve adipose function and achieve improvements in overall metabolic health.
Topics: Adipocytes; Adipose Tissue; Adipose Tissue, White; Homeostasis; Humans; Mitochondria
PubMed: 34810062
DOI: 10.1016/j.tcb.2021.10.008 -
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