Advances in Adipose Tissue Biology

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Metabolism".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 7064

Special Issue Editor

1. Department of Endocrinology, Division of Medicine, Tan Tock Seng Hospital, Singapore 308433, Singapore
2. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore
3. Singapore Institute for Clinical Sciences, Brenner Centre for Molecular Medicine, Agency for Science, Technology and Research (A*STAR), Singapore 117609, Singapore
4. Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore 169857, Singapore
5. Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Interests: adipocyte biology; metabolic syndrome/diabetes; thyroidology; endocrine manifestations of systemic disorders; mathematical modeling of endocrine physiology
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Special Issue Information

Dear Colleagues,

Much progress in the past two decades has revolutionized our understanding of adipose tissues in the body. Fat is no longer simply thought of as a homogeneous organ that shields the body from cold and mechanical shocks. Once believed to be an inert fat depot with few biological properties, recent advances facilitated by cutting-edge ‘omics’ and other novel scientific methodologies have probed and elucidated the pleiotropic nature of this organ at the molecular level. Even its role in fat storage can predispose adipose tissue toward pathological trajectories; new evidence supports fat expandability defects and ectopic fat deposition as drivers of metabolic disease. Apart from regulating triglyceride energy storage, adipocytes secrete numerous bioactive cargoes housed within extracellular vesicles released from their cell membranes into the circulation, thereby exerting a broad range of distant endocrine effects elsewhere in the body. In addition, the plasticity of adipocytes has implications in remodeling and tissue engineering for obesity treatment aimed at the browning of white adipose tissues. We now appreciate how heterogeneity existing within adipose tissues orchestrates complex dynamics, signaling and feedbacks in the maintenance of health and disease. Notably, adipocytes have been demonstrated to act as stromal cells in the tumor microenvironment, with molecular crosstalk proven to promote cancer-cell proliferation, migration, invasion and metastasis. The disruption of adipocyte homeostasis by both genes and the environment with consequent metabolic dysfunction contributes to system-wide inflammation that underlies many non-communicable chronic disease pandemics, such as non-alcoholic fatty liver disease, obesity, diabetes, cardiovascular diseases and even cancers.

The study of adipose biology has thus entered a new era. In this respect, this Special Issue aims to showcase scientific advances and fascinating discoveries that may not only be translated to the bedside and address the burgeoning toll exacted by obesity, diabetes and the like, but also further propel both basic scientists and clinical researchers to greater breakthroughs. Toward that end, the articles in this Special Issue will hopefully serve as an inspiring resource for all who wish to be current in this most fascinating biological field.

Dr. Melvin K.S. Leow
Guest Editor

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Keywords

  • adipocyte differentiation, progenitors and stem cells
  • adipokines, myokines, hepatokines, cytokines, cellular signaling and molecular crosstalk
  • white adipose tissue (WAT) and brown adipose tissue (BAT)
  • beige fat and browning of WAT
  • research techniques and methodologies
  • diagnostics and therapeutics, genomics, metabolomics, other ‘omics’ technologies
  • metabolic syndrome, obesity, insulin resistance, cancer

Published Papers (4 papers)

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Research

17 pages, 4044 KiB  
Article
Subcutaneous Adipose Tissue Transcriptome Highlights Specific Expression Profiles in Severe Pediatric Obesity: A Pilot Study
Cells 2023, 12(8), 1105; https://doi.org/10.3390/cells12081105 - 07 Apr 2023
Viewed by 1427
Abstract
The prevalence of pediatric obesity is rising rapidly worldwide, and “omic” approaches are helpful in investigating the molecular pathophysiology of obesity. This work aims to identify transcriptional differences in the subcutaneous adipose tissue (scAT) of children with overweight (OW), obesity (OB), or severe [...] Read more.
The prevalence of pediatric obesity is rising rapidly worldwide, and “omic” approaches are helpful in investigating the molecular pathophysiology of obesity. This work aims to identify transcriptional differences in the subcutaneous adipose tissue (scAT) of children with overweight (OW), obesity (OB), or severe obesity (SV) compared with those of normal weight (NW). Periumbilical scAT biopsies were collected from 20 male children aged 1–12 years. The children were stratified into the following four groups according to their BMI z-scores: SV, OB, OW, and NW. scAT RNA-Seq analyses were performed, and a differential expression analysis was conducted using the DESeq2 R package. A pathways analysis was performed to gain biological insights into gene expression. Our data highlight the significant deregulation in both coding and non-coding transcripts in the SV group when compared with the NW, OW, and OB groups. A KEGG pathway analysis showed that coding transcripts were mainly involved in lipid metabolism. A GSEA analysis revealed the upregulation of lipid degradation and metabolism in SV vs. OB and SV vs. OW. Bioenergetic processes and the catabolism of branched-chain amino acids were upregulated in SV compared with OB, OW, and NW. In conclusion, we report for the first time that a significant transcriptional deregulation occurs in the periumbilical scAT of children with severe obesity compared with those of normal weight or those with overweight or mild obesity. Full article
(This article belongs to the Special Issue Advances in Adipose Tissue Biology)
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15 pages, 4388 KiB  
Article
Chordin-like 1, a Novel Adipokine, Markedly Promotes Adipogenesis and Lipid Accumulation
Cells 2023, 12(4), 624; https://doi.org/10.3390/cells12040624 - 15 Feb 2023
Cited by 1 | Viewed by 1069
Abstract
White adipose tissue serves as a metabolically dynamic organ that can synthesize and secrete biologically active compounds such as adipokines as well as a caloric reservoir for maintaining energy homeostasis. Adipokines are involved in diverse biological and physiological processes and there have been [...] Read more.
White adipose tissue serves as a metabolically dynamic organ that can synthesize and secrete biologically active compounds such as adipokines as well as a caloric reservoir for maintaining energy homeostasis. Adipokines are involved in diverse biological and physiological processes and there have been extensive attempts to characterize the effects of over two dozen adipokines. However, many of these adipokines are produced by not only adipose tissue, but also other tissues. Therefore, investigations into the effects of adipokines on physiological functions have been challenged. In this regard, we aimed to identify a new secreted protein that is encoded by genes specifically expressed in white adipose tissue through analysis of multi-tissue transcriptome and protein expression. As a result, we report a novel adipokine that is encoded by the adipose-specific gene, chordin-like 1 (Chrdl1), which is specifically expressed in white adipose tissue in mice; this expression pattern was conserved in the human orthologous CHRDL1 gene. The expression of Chrdl1 was enriched in fat cells and developmentally regulated in vitro and in vivo, and moreover, its retrovirus-mediated overexpression and recombinant protein treatment led to markedly increased adipogenesis. Further pathway enrichment analysis revealed enriched pathways related to lipogenesis and adipogenic signaling. Our findings support a pro-adipogenic role of CHRDL1 as a new adipokine and pave the way toward animal studies and future research on its clinical implications and development of anti-obesity therapy. Full article
(This article belongs to the Special Issue Advances in Adipose Tissue Biology)
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22 pages, 4017 KiB  
Article
Profiling of G-Protein Coupled Receptors in Adipose Tissue and Differentiating Adipocytes Offers a Translational Resource for Obesity/Metabolic Research
Cells 2023, 12(3), 377; https://doi.org/10.3390/cells12030377 - 19 Jan 2023
Cited by 3 | Viewed by 2377
Abstract
G protein-coupled receptors (GPCRs) are expressed essentially on all cells, facilitating cellular responses to external stimuli, and are involved in nearly every biological process. Several members of this family play significant roles in the regulation of adipogenesis and adipose metabolism. However, the expression [...] Read more.
G protein-coupled receptors (GPCRs) are expressed essentially on all cells, facilitating cellular responses to external stimuli, and are involved in nearly every biological process. Several members of this family play significant roles in the regulation of adipogenesis and adipose metabolism. However, the expression and functional significance of a vast number of GPCRs in adipose tissue are unknown. We used a high-throughput RT-PCR panel to determine the expression of the entire repertoire of non-sensory GPCRs in mouse white, and brown adipose tissue and assess changes in their expression during adipogenic differentiation of murine adipocyte cell line, 3T3-L1. In addition, the expression of GPCRs in subcutaneous adipose tissues from lean, obese, and diabetic human subjects and in adipocytes isolated from regular chow and high-fat fed mice were evaluated by re-analyzing RNA-sequencing data. We detected a total of 292 and 271 GPCRs in mouse white and brown adipose tissue, respectively. There is a significant overlap in the expression of GPCRs between the two adipose tissue depots, but several GPCRs are specifically expressed in one of the two tissue types. Adipogenic differentiation of 3T3-L1 cells had a profound impact on the expression of several GPCRs. RNA sequencing of subcutaneous adipose from healthy human subjects detected 255 GPCRs and obesity significantly changed the expression of several GPCRs in adipose tissue. High-fat diet had a significant impact on adipocyte GPCR expression that was similar to human obesity. Finally, we report several highly expressed GPCRs with no known role in adipose biology whose expression was significantly altered during adipogenic differentiation, and/or in the diseased human subjects. These GPCRs could play an important role in adipose metabolism and serve as a valuable translational resource for obesity and metabolic research. Full article
(This article belongs to the Special Issue Advances in Adipose Tissue Biology)
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13 pages, 19047 KiB  
Communication
Regulation of Adipose Progenitor Cell Expansion in a Novel Micro-Physiological Model of Human Adipose Tissue Mimicking Fibrotic and Pro-Inflammatory Microenvironments
Cells 2022, 11(18), 2798; https://doi.org/10.3390/cells11182798 - 07 Sep 2022
Cited by 2 | Viewed by 1583
Abstract
The expansion of adipose progenitor cells (APCs) plays an important role in the regeneration of the adipose tissue in physiological and pathological situations. The major role of CD26-expressing APCs in the generation of adipocytes has recently been highlighted, revealing that the CD26 APC [...] Read more.
The expansion of adipose progenitor cells (APCs) plays an important role in the regeneration of the adipose tissue in physiological and pathological situations. The major role of CD26-expressing APCs in the generation of adipocytes has recently been highlighted, revealing that the CD26 APC subtype displays features of multipotent stem cells, giving rise to CD54- and CD142-expressing preadipocytes. However, a relevant human in vitro model to explore the regulation of the APC subpopulation expansion in lean and obese adipose tissue microenvironments is still lacking. In this work, we describe a novel adipose tissue model, named ExAdEx, that can be obtained from cosmetic surgery wastes. ExAdEx products are adipose tissue units maintaining the characteristics and organization of adipose tissue as it presents in vivo. The model was viable and metabolically active for up to two months and could adopt a pathological-like phenotype. The results revealed that inflammatory and fibrotic microenvironments differentially regulated the expansion of the CD26 APC subpopulation and its CD54 and CD142 APC progenies. The approach used significantly improves the method of generating adipose tissue models, and ExAdEx constitutes a relevant model that could be used to identify pathways promoting the expansion of APCs in physiological and pathological microenvironments. Full article
(This article belongs to the Special Issue Advances in Adipose Tissue Biology)
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