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Clinical Science (London, England :... Oct 2019Adipose tissues collectively as an endocrine organ and energy storage are crucial for systemic metabolic homeostasis. The major cell type in the adipose tissue, the... (Review)
Review
Adipose tissues collectively as an endocrine organ and energy storage are crucial for systemic metabolic homeostasis. The major cell type in the adipose tissue, the adipocytes or fat cells, are remarkably plastic and can increase or decrease their size and number to adapt to changes in systemic or local metabolism. Changes in adipocyte size occur through hypertrophy or atrophy, and changes in cell numbers mainly involve de novo generation of new cells or death of existing cells. Recently, dedifferentiation, whereby a mature adipocyte is reverted to an undifferentiated progenitor-like status, has been reported as a mechanism underlying adipocyte plasticity. Dedifferentiation of mature adipocytes has been observed under both physiological and pathological conditions. This review covers several aspects of adipocyte dedifferentiation, its relevance to adipose tissue function, molecular pathways that drive dedifferentiation, and the potential of therapeutic targeting adipocyte dedifferentiation in human health and metabolic diseases.
Topics: Adipocytes; Adipose Tissue; Animals; Antineoplastic Agents; Breast Neoplasms; Cell Communication; Cell Dedifferentiation; Cell Plasticity; Cells, Cultured; Cellular Microenvironment; Humans; Lactation; Metabolic Diseases
PubMed: 31654064
DOI: 10.1042/CS20190128 -
The Journal of Clinical Investigation Jul 2019Development of novel and effective therapeutics for treating various cancers is probably the most congested and challenging enterprise of pharmaceutical companies.... (Review)
Review
Development of novel and effective therapeutics for treating various cancers is probably the most congested and challenging enterprise of pharmaceutical companies. Diverse drugs targeting malignant and nonmalignant cells receive clinical approval each year from the FDA. Targeting cancer cells and nonmalignant cells unavoidably changes the tumor microenvironment, and cellular and molecular components relentlessly alter in response to drugs. Cancer cells often reprogram their metabolic pathways to adapt to environmental challenges and facilitate survival, proliferation, and metastasis. While cancer cells' dependence on glycolysis for energy production is well studied, the roles of adipocytes and lipid metabolic reprogramming in supporting cancer growth, metastasis, and drug responses are less understood. This Review focuses on emerging mechanisms involving adipocytes and lipid metabolism in altering the response to cancer treatment. In particular, we discuss mechanisms underlying cancer-associated adipocytes and lipid metabolic reprogramming in cancer drug resistance.
Topics: Adipocytes; Animals; Drug Resistance, Neoplasm; Glycolysis; Humans; Lipid Metabolism; Neoplasms; Tumor Microenvironment
PubMed: 31264969
DOI: 10.1172/JCI127201 -
Annual Review of Biochemistry 2012Excessive caloric intake without a rise in energy expenditure promotes adipocyte hyperplasia and adiposity. The rise in adipocyte number is triggered by signaling... (Review)
Review
Excessive caloric intake without a rise in energy expenditure promotes adipocyte hyperplasia and adiposity. The rise in adipocyte number is triggered by signaling factors that induce conversion of mesenchymal stem cells (MSCs) to preadipocytes that differentiate into adipocytes. MSCs, which are recruited from the vascular stroma of adipose tissue, provide an unlimited supply of adipocyte precursors. Members of the BMP and Wnt families are key mediators of stem cell commitment to produce preadipocytes. Following commitment, exposure of growth-arrested preadipocytes to differentiation inducers [insulin-like growth factor 1 (IGF1), glucocorticoid, and cyclic AMP (cAMP)] triggers DNA replication and reentry into the cell cycle (mitotic clonal expansion). Mitotic clonal expansion involves a transcription factor cascade, followed by the expression of adipocyte genes. Critical to these events are phosphorylations of the transcription factor CCATT enhancer-binding protein β (C/EBPβ) by MAP kinase and GSK3β to produce a conformational change that gives rise to DNA-binding activity. "Activated" C/EBPβ then triggers transcription of peroxisome proliferator-activated receptor-γ (PPARγ) and C/EBPα, which in turn coordinately activate genes whose expression produces the adipocyte phenotype.
Topics: Adipocytes; Adipogenesis; Animals; Humans; Signal Transduction; Stem Cells; Transcription Factors
PubMed: 22463691
DOI: 10.1146/annurev-biochem-052110-115718 -
Cancer Metastasis Reviews Sep 2022Many epithelial tumors grow in the vicinity of or metastasize to adipose tissue. As tumors develop, crosstalk between adipose tissue and cancer cells leads to changes in... (Review)
Review
Many epithelial tumors grow in the vicinity of or metastasize to adipose tissue. As tumors develop, crosstalk between adipose tissue and cancer cells leads to changes in adipocyte function and paracrine signaling, promoting a microenvironment that supports tumor growth. Over the last decade, it became clear that tumor cells co-opt adipocytes in the tumor microenvironment, converting them into cancer-associated adipocytes (CAA). As adipocytes and cancer cells engage, a metabolic symbiosis ensues that is driven by bi-directional signaling. Many cancers (colon, breast, prostate, lung, ovarian cancer, and hematologic malignancies) stimulate lipolysis in adipocytes, followed by the uptake of fatty acids (FA) from the surrounding adipose tissue. The FA enters the cancer cell through specific fatty acid receptors and binding proteins (e.g., CD36, FATP1) and are used for membrane synthesis, energy metabolism (β-oxidation), or lipid-derived cell signaling molecules (derivatives of arachidonic and linolenic acid). Therefore, blocking adipocyte-derived lipid uptake or lipid-associated metabolic pathways in cancer cells, either with a single agent or in combination with standard of care chemotherapy, might prove to be an effective strategy against cancers that grow in lipid-rich tumor microenvironments.
Topics: Adipocytes; Adipose Tissue; Fatty Acids; Female; Humans; Ovarian Neoplasms; Tumor Microenvironment
PubMed: 35941408
DOI: 10.1007/s10555-022-10059-x -
Nature Reviews. Molecular Cell Biology Dec 2006Improved knowledge of all aspects of adipose biology will be required to counter the burgeoning epidemic of obesity. Interest in adipogenesis has increased markedly over... (Review)
Review
Improved knowledge of all aspects of adipose biology will be required to counter the burgeoning epidemic of obesity. Interest in adipogenesis has increased markedly over the past few years with emphasis on the intersection between extracellular signals and the transcriptional cascade that regulates adipocyte differentiation. Many different events contribute to the commitment of a mesenchymal stem cell to the adipocyte lineage including the coordination of a complex network of transcription factors, cofactors and signalling intermediates from numerous pathways.
Topics: Adipocytes; Adipogenesis; Animals; Humans; Mesenchymal Stem Cells; Obesity; Signal Transduction; Transcription Factors; Transcription, Genetic
PubMed: 17139329
DOI: 10.1038/nrm2066 -
Cellular and Molecular Life Sciences :... Jan 2020Adipose tissue is located in discrete depots that are differentially associated with elevated risk of metabolic complications, with fat accretion in visceral depots... (Review)
Review
Adipose tissue is located in discrete depots that are differentially associated with elevated risk of metabolic complications, with fat accretion in visceral depots being most detrimental to metabolic health. Currently, the regulation of specific adipose depot expansion, by adipocyte hypertrophy and hyperplasia and consequently fat distribution, is not well understood. However, a growing body of evidence from in vitro investigations indicates that mature adipocytes secrete factors that modulate the proliferation and differentiation of progenitor, adipose-derived stem cells (ADSCs). It is therefore plausible that endocrine communication between adipocytes and ADSCs located in different depots influences fat distribution, and may therefore contribute to the adverse health outcomes associated with visceral adiposity. This review will explore the available evidence of paracrine and endocrine crosstalk between mature adipocytes and ADSCs that affects adipogenesis, as a better understanding of the regulatory roles of the extracellular signalling mechanisms within- and between adipose depots may profoundly change the way we view adipose tissue growth in obesity and related comorbidities.
Topics: Adipocytes; Adipogenesis; Animals; Cell Communication; Humans; Obesity; Paracrine Communication; Signal Transduction; Stem Cells
PubMed: 31352534
DOI: 10.1007/s00018-019-03256-5 -
Frontiers in Endocrinology 2020Maintenance of adipocyte precursors is critical for regulating metabolism and preventing obesity related disease. These precursors have been immortalized and studied in... (Review)
Review
Maintenance of adipocyte precursors is critical for regulating metabolism and preventing obesity related disease. These precursors have been immortalized and studied in cellular models as well as-more recently-in animal models. However, little is known about adipocyte precursors from animals of different ages. Most research has focused on adipocyte precursors during obesity. This review goes over the most recent reports of adipocyte precursors during development and in adulthood. Some of these new analyses are due to new techniques such as single cell-RNA sequencing and temporally controlled lineage tracing. With these tools, we have been able to further our understanding of adipocyte precursor lineages and their different regulatory mechanisms. As we learn more about adipocyte precursor plasticity and regulation, we can hope to use this knowledge for future clinical applications.
Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Cell Differentiation; Humans; Obesity; Single-Cell Analysis
PubMed: 33679601
DOI: 10.3389/fendo.2020.613606 -
Cell Stem Cell Jun 2017Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we...
Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation. Conversely, bone-resident cells committed to the adipocytic lineage inhibit hematopoiesis and bone healing, potentially by producing excessive amounts of Dipeptidyl peptidase-4, a protease that is a target of diabetes therapies. These studies delineate the molecular identity of the bone-resident adipocytic lineage, and they establish its involvement in age-dependent dysfunction of bone and hematopoietic regeneration.
Topics: Adipocytes; Aging; Animals; Bone Marrow; Bone Regeneration; Dipeptidyl Peptidase 4; Hematopoiesis; Mice; Mice, Transgenic; Obesity
PubMed: 28330582
DOI: 10.1016/j.stem.2017.02.009 -
Nature Reviews. Molecular Cell Biology Apr 2019Obesity is characterized by increased adipose tissue mass and has been associated with a strong predisposition towards metabolic diseases and cancer. Thus, it... (Review)
Review
Obesity is characterized by increased adipose tissue mass and has been associated with a strong predisposition towards metabolic diseases and cancer. Thus, it constitutes a public health issue of major proportion. The expansion of adipose depots can be driven either by the increase in adipocyte size (hypertrophy) or by the formation of new adipocytes from precursor differentiation in the process of adipogenesis (hyperplasia). Notably, adipocyte expansion through adipogenesis can offset the negative metabolic effects of obesity, and the mechanisms and regulators of this adaptive process are now emerging. Over the past several years, we have learned a considerable amount about how adipocyte fate is determined and how adipogenesis is regulated by signalling and systemic factors. We have also gained appreciation that the adipogenic niche can influence tissue adipogenic capability. Approaches aimed at increasing adipogenesis over adipocyte hypertrophy can now be explored as a means to treat metabolic diseases.
Topics: Adipocytes; Adipogenesis; Animals; Cell Differentiation; Health; Humans; Obesity; Signal Transduction
PubMed: 30610207
DOI: 10.1038/s41580-018-0093-z -
Development (Cambridge, England) Apr 2019Adipose tissue is composed of anatomically distinct depots that mediate several important aspects of energy homeostasis. The past two decades have witnessed increased... (Review)
Review
Adipose tissue is composed of anatomically distinct depots that mediate several important aspects of energy homeostasis. The past two decades have witnessed increased research effort to elucidate the ontogenetic basis of adipose form and function. In this Review, we discuss advances in our understanding of adipose tissue development with particular emphasis on the embryonic patterning of depot-specific adipocyte lineages and adipocyte differentiation Micro-environmental cues and other factors that influence cell identity and cell behavior at various junctures in the adipocyte lineage hierarchy are also considered.
Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Humans; Obesity
PubMed: 30948523
DOI: 10.1242/dev.172098