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Physiology (Bethesda, Md.) Mar 2020Adipose-derived stem cells (ASCs) can self-renew and differentiate along multiple cell lineages. ASCs are also potently anti-inflammatory due to their inherent ability... (Review)
Review
Adipose-derived stem cells (ASCs) can self-renew and differentiate along multiple cell lineages. ASCs are also potently anti-inflammatory due to their inherent ability to regulate the immune system by secreting anti-inflammatory cytokines and growth factors that play a crucial role in the pathology of many diseases, including multiple sclerosis, diabetes mellitus, Crohn's, SLE, and graft-versus-host disease. The immunomodulatory effects and mechanisms of action of ASCs on pathological conditions are reviewed here.
Topics: Adipose Tissue; Animals; Cell Differentiation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Stem Cells
PubMed: 32027561
DOI: 10.1152/physiol.00021.2019 -
Cell Reports Jul 2022The importance of defining cell-type-specific genes is well acknowledged. Technological advances facilitate high-resolution sequencing of single cells, but practical...
The importance of defining cell-type-specific genes is well acknowledged. Technological advances facilitate high-resolution sequencing of single cells, but practical challenges remain. Adipose tissue is composed primarily of adipocytes, large buoyant cells requiring extensive, artefact-generating processing for separation and analysis. Thus, adipocyte data are frequently absent from single-cell RNA sequencing (scRNA-seq) datasets, despite being the primary functional cell type. Here, we decipher cell-type-enriched transcriptomes from unfractionated human adipose tissue RNA-seq data. We profile all major constituent cell types, using 527 visceral adipose tissue (VAT) or 646 subcutaneous adipose tissue (SAT) samples, identifying over 2,300 cell-type-enriched transcripts. Sex-subset analysis uncovers a panel of male-only cell-type-enriched genes. By resolving expression profiles of genes differentially expressed between SAT and VAT, we identify mesothelial cells as the primary driver of this variation. This study provides an accessible method to profile cell-type-enriched transcriptomes using bulk RNA-seq, generating a roadmap for adipose tissue biology.
Topics: Adipose Tissue; Gene Expression Profiling; Humans; Intra-Abdominal Fat; Male; Subcutaneous Fat; Transcriptome
PubMed: 35830816
DOI: 10.1016/j.celrep.2022.111046 -
Cell Reports Jun 2022In hepatocytes, peroxisome proliferator-activated receptor α (PPARα) orchestrates a genomic and metabolic response required for homeostasis during fasting. This...
In hepatocytes, peroxisome proliferator-activated receptor α (PPARα) orchestrates a genomic and metabolic response required for homeostasis during fasting. This includes the biosynthesis of ketone bodies and of fibroblast growth factor 21 (FGF21). Here we show that in the absence of adipose triglyceride lipase (ATGL) in adipocytes, ketone body and FGF21 production is impaired upon fasting. Liver gene expression analysis highlights a set of fasting-induced genes sensitive to both ATGL deletion in adipocytes and PPARα deletion in hepatocytes. Adipose tissue lipolysis induced by activation of the β-adrenergic receptor also triggers such PPARα-dependent responses not only in the liver but also in brown adipose tissue (BAT). Intact PPARα activity in hepatocytes is required for the cross-talk between adipose tissues and the liver during fat mobilization.
Topics: Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Hepatocytes; Ketone Bodies; Lipolysis; PPAR alpha
PubMed: 35675775
DOI: 10.1016/j.celrep.2022.110910 -
Cell Metabolism Mar 2022In mammals, white adipose tissues are largely divided into visceral epididymal adipose tissue (EAT) and subcutaneous inguinal adipose tissue (IAT) with distinct...
In mammals, white adipose tissues are largely divided into visceral epididymal adipose tissue (EAT) and subcutaneous inguinal adipose tissue (IAT) with distinct metabolic properties. Although emerging evidence suggests that subpopulations of adipose stem cells (ASCs) would be important to explain fat depot differences, ASCs of two fat depots have not been comparatively investigated. Here, we characterized heterogeneous ASCs and examined the effects of intrinsic and tissue micro-environmental factors on distinct ASC features. We demonstrated that ASC subpopulations in EAT and IAT exhibited different molecular features with three adipogenic stages. ASC transplantation experiments revealed that intrinsic ASC features primarily determined their adipogenic potential. Upon obesogenic stimuli, EAT-specific SDC1 ASCs promoted fibrotic remodeling, whereas IAT-specific CXCL14 ASCs suppressed macrophage infiltration. Moreover, IAT-specific BST2 ASCs exhibited a high potential to become beige adipocytes. Collectively, our data broaden the understanding of ASCs with new insights into the origin of white fat depot differences.
Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Mammals; Stem Cells; Subcutaneous Fat
PubMed: 35021043
DOI: 10.1016/j.cmet.2021.11.014 -
Redox Biology Jul 2021Loss of perivascular adipose tissue (PVAT) impairs endothelial function and enhances atherosclerosis. However, the roles of PVAT thermoregulation in vascular...
Loss of perivascular adipose tissue (PVAT) impairs endothelial function and enhances atherosclerosis. However, the roles of PVAT thermoregulation in vascular inflammation and the development of atherosclerosis remains unclear. Bone morphogenetic protein 4 (BMP4) transforms white adipocyte to beige adipocyte, while promotes a brown-to-white shift in inter-scapular brown adipose tissue (BAT). Here, we found that knockdown of BMP4 in PVAT reduced expression of brown adipocyte-characteristic genes and increased endothelial inflammation in vitro co-culture system. Ablating BMP4 expression either in adipose tissues or specifically in BAT in ApoE mice demonstrated a marked exacerbation of atherosclerotic plaque formation in vivo. We further demonstrated that proinflammatory factors (especially IL-1β) increased in the supernatant of BMP4 knockdown adipocytes. Overexpression of BMP4 in adipose tissues promotes browning of PVAT and protects against atherosclerosis in ApoE mice. These findings uncover an organ crosstalk between PVAT and blood endothelial cells that is engaged in atherosclerosis.
Topics: Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Anti-Inflammatory Agents; Atherosclerosis; Bone Morphogenetic Protein 4; Endothelial Cells; Mice
PubMed: 33895484
DOI: 10.1016/j.redox.2021.101979 -
Cell Reports Apr 2023Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are...
Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood, and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses, we find that 11 days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition and increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism.
Topics: Male; Mice; Animals; Motor Activity; Adipose Tissue, White; Adaptation, Physiological; Acclimatization; Transcription Factors; Adipose Tissue, Brown; Adipose Tissue; Mice, Inbred C57BL; Cell Adhesion Molecules, Neuronal
PubMed: 37058410
DOI: 10.1016/j.celrep.2023.112392 -
Frontiers in Endocrinology 2022
Topics: Adipose Tissue; Intra-Abdominal Fat
PubMed: 36060968
DOI: 10.3389/fendo.2022.999188 -
Cells Aug 2020Adipose tissue is a rich, ubiquitous, and easily accessible source for multipotent mesenchymal stromal/stem cells (MSCs), so-called adipose-derived stromal/stem cells...
Adipose tissue is a rich, ubiquitous, and easily accessible source for multipotent mesenchymal stromal/stem cells (MSCs), so-called adipose-derived stromal/stem cells (ASCs) [...].
Topics: Adipose Tissue; Cell Differentiation; Humans; Stromal Cells
PubMed: 32872606
DOI: 10.3390/cells9091997 -
Frontiers in Endocrinology 2020
Topics: Adipose Tissue; Aging; Humans; Longevity
PubMed: 32982974
DOI: 10.3389/fendo.2020.00583 -
Frontiers in Endocrinology 2020Adipose tissue is a key nutrient-sensing depot that regulates excess energy storage and consumption. Adipocytes, the key components of the adipose tissue, have unique... (Review)
Review
Adipose tissue is a key nutrient-sensing depot that regulates excess energy storage and consumption. Adipocytes, the key components of the adipose tissue, have unique ability to store excess energy in the form of triglycerides, sense systemic energy demands, and secrete factors (lipids, peptides, cytokines, and adipokines) to regulate other metabolic tissues. The presence of various types of adipocytes (white, brown, and beige) characterized by the number/size of lipid droplets, mitochondrial density, and thermogenic capacity, further highlights how intricate is the communication of these cell-types with other metabolic tissues to sense nutrients. In obesity the inherent capacity of adipose tissue to store and sense nutrients is compromised, causing spillover of the intermediate lipid metabolites into circulation and resulting in their ectopic deposition in tissues not suitable for lipid storage, a phenomenon known as lipotoxicity. This results in a spectrum of cellular dysfunction, that underlies various metabolic diseases. Of the numerous lipid classes implicated in eliciting lipotoxicity, sphingolipid: ceramides are among the most deleterious as they modulate signaling pathways involved in regulating glucose metabolism, triglyceride synthesis, apoptosis, and fibrosis. Notably, recent experimental studies have strongly implicated ceramides in the development of numerous metabolic diseases such as insulin resistance, diabetes, cardiomyopathy, hepatic-steatosis, and atherosclerosis. Herein we discuss and summarizes recent findings that implicate ceramides as a key contributor to adipocyte dysfunction underlying metabolic diseases and how depletion of ceramides can be exploited to improve metabolic health.
Topics: Adipose Tissue; Animals; Ceramides; Humans; Lipid Metabolism; Metabolic Diseases; Thermogenesis
PubMed: 32636806
DOI: 10.3389/fendo.2020.00407