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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 -
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 -
The Journal of Clinical Investigation Jun 2011To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited... (Review)
Review
To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited capacity to expand in a non-transformed state. As such, the tissue requires potent mechanisms to remodel, acutely and chronically. Adipocytes can rapidly reach the diffusional limit of oxygen during growth; hypoxia is therefore an early determinant that limits healthy expansion. Proper expansion requires a highly coordinated response among many different cell types, including endothelial precursor cells, immune cells, and preadipocytes. There are therefore remarkable similarities between adipose expansion and growth of solid tumors, a phenomenon that presents both an opportunity and a challenge, since pharmacological interventions supporting healthy adipose tissue adaptation can also facilitate tumor growth.
Topics: Adaptation, Physiological; Adipocytes; Adipose Tissue; Animals; Cell Division; Cell Hypoxia; Cell Size; Endothelial Cells; Energy Metabolism; Extracellular Matrix; Fatty Acids; Humans; Inflammation; Macrophages; Mice; Mice, Transgenic; Neovascularization, Physiologic; Obesity; Weight Loss
PubMed: 21633177
DOI: 10.1172/JCI45887 -
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 -
Cold Spring Harbor Perspectives in... Sep 2012Adipose tissue is an important site for lipid storage, energy homeostasis, and whole-body insulin sensitivity. It is important to understand the mechanisms involved in... (Review)
Review
Adipose tissue is an important site for lipid storage, energy homeostasis, and whole-body insulin sensitivity. It is important to understand the mechanisms involved in adipose tissue development and function, which can be regulated by the endocrine actions of various peptide and steroid hormones. Recent studies have revealed that white and brown adipocytes can be derived from distinct precursor cells. This review will focus on transcriptional control of adipogenesis and its regulation by several endocrine hormones. The general functions and cellular origins of adipose tissue and how the modulation of adipocyte development pertains to metabolic disease states will also be considered.
Topics: Adipocytes, Brown; Adipocytes, White; Adipogenesis; Adipose Tissue; Animals; Gene Regulatory Networks; Humans; Metabolic Diseases; Models, Biological; Signal Transduction
PubMed: 22952395
DOI: 10.1101/cshperspect.a008417 -
Journal of Lipid Research Oct 2019The breakthrough discoveries of leptin and adiponectin more than two decades ago led to a widespread recognition of adipose tissue as an endocrine organ. Many more... (Review)
Review
The breakthrough discoveries of leptin and adiponectin more than two decades ago led to a widespread recognition of adipose tissue as an endocrine organ. Many more adipose tissue-secreted signaling mediators (adipokines) have been identified since then, and much has been learned about how adipose tissue communicates with other organs of the body to maintain systemic homeostasis. Beyond proteins, additional factors, such as lipids, metabolites, noncoding RNAs, and extracellular vesicles (EVs), released by adipose tissue participate in this process. Here, we review the diverse signaling mediators and mechanisms adipose tissue utilizes to relay information to other organs. We discuss recently identified adipokines (proteins, lipids, and metabolites) and briefly outline the contributions of noncoding RNAs and EVs to the ever-increasing complexities of adipose tissue inter-organ communication. We conclude by reflecting on central aspects of adipokine biology, namely, the contribution of distinct adipose tissue depots and cell types to adipokine secretion, the phenomenon of adipokine resistance, and the capacity of adipose tissue to act both as a source and sink of signaling mediators.
Topics: Adiponectin; Adipose Tissue; Animals; Humans; Leptin; Lipid Metabolism; Signal Transduction
PubMed: 31209153
DOI: 10.1194/jlr.R094060 -
Physiological Reviews Jul 1998The adipocyte plays a critical role in energy balance. Adipose tissue growth involves an increase in adipocyte size and the formation of new adipocytes from precursor... (Review)
Review
The adipocyte plays a critical role in energy balance. Adipose tissue growth involves an increase in adipocyte size and the formation of new adipocytes from precursor cells. For the last 20 years, the cellular and molecular mechanisms of adipocyte differentiation have been extensively studied using preadipocyte culture systems. Committed preadipocytes undergo growth arrest and subsequent terminal differentiation into adipocytes. This is accompanied by a dramatic increase in expression of adipocyte genes including adipocyte fatty acid binding protein and lipid-metabolizing enzymes. Characterization of regulatory regions of adipose-specific genes has led to the identification of the transcription factors peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer binding protein (C/EBP), which play a key role in the complex transcriptional cascade during adipocyte differentiation. Growth and differentiation of preadipocytes is controlled by communication between individual cells or between cells and the extracellular environment. Various hormones and growth factors that affect adipocyte differentiation in a positive or negative manner have been identified. In addition, components involved in cell-cell or cell-matrix interactions such as preadipocyte factor-1 and extracellular matrix proteins are also pivotal in regulating the differentiation process. Identification of these molecules has yielded clues to the biochemical pathways that ultimately result in transcriptional activation via PPAR-gamma and C/EBP. Studies on the regulation of the these transcription factors and the mode of action of various agents that influence adipocyte differentiation will reveal the physiological and pathophysiological mechanisms underlying adipose tissue development.
Topics: Adipocytes; Adipose Tissue; Animals; Cell Differentiation; Humans
PubMed: 9674695
DOI: 10.1152/physrev.1998.78.3.783 -
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