-
European Journal of Cell Biology Sep 2023Although phenotypically different, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) are able to produce heat through non-shivering thermogenesis due...
Although phenotypically different, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) are able to produce heat through non-shivering thermogenesis due to the presence of mitochondrial uncoupling protein 1 (UCP1). The appearance of thermogenically active beige adipocytes in iWAT is known as browning. Both brown and beige cells originate from mesenchymal stem cells (MSCs), and in culture conditions a browning response can be induced with hypothermia (i.e. 32 °C) during which nuclear leptin immunodetection was observed. The central role of leptin in regulating food intake and energy consumption is well recognised, but its importance in the browning process at the cellular level is unclear. Here, immunocytochemical analysis of MSC-derived adipocytes established nuclear localization of both leptin and leptin receptor suggesting an involvement of the leptin pathway in the browning response. In order to elucidate whether leptin modulates the expression of brown and beige adipocyte markers, BAT and iWAT samples from leptin-deficient (ob/ob) mice were analysed and exhibited reduced brown/beige marker expression compared to wild-type controls. When MSCs were isolated and differentiated into adipocytes, leptin deficiency was observed to induce a white phenotype, especially when incubated at 32 °C. These adaptations were accompanied with morphological signs of impaired adipogenic differentiation. Overall, our results indicate that leptin supports adipocyte browning and suggest a potential role for leptin in adipogenesis and browning.
Topics: Animals; Mice; Adipocytes; Adipocytes, Brown; Adipogenesis; Cell Differentiation; Leptin; Signal Transduction
PubMed: 37467572
DOI: 10.1016/j.ejcb.2023.151342 -
Obesity Reviews : An Official Journal... Feb 2021Obesity, defined as excessive fat accumulation, is strongly associated with metabolic diseases and cancer, and its prevalence is rising worldwide. Thus, understanding... (Review)
Review
Obesity, defined as excessive fat accumulation, is strongly associated with metabolic diseases and cancer, and its prevalence is rising worldwide. Thus, understanding the molecular mechanism of adipogenesis is of fundamental significance. Epigenetic modifications play important roles in regulating adipogenesis. N -methyladenosine (m A), the most prevalent and abundant mRNA modification in eukaryotic cells, modulates multiple aspects of RNA metabolism, including mRNA stability, translation, splicing and export. Recent studies indicate that m A methylation plays important roles in modulating gene expression and signal pathways in various physiologic processes and diseases. Notably, the significant function and regulatory mechanisms of m A in adipogenesis are now emerging. In this review, we summarize recent studies that elucidate the vital roles of m A modifications in regulating adipogenesis and adipose tissue expansion. Furthermore, we highlight the nutritional regulation of m A methylation and adipogenesis, which may prove a novel therapeutic strategy to fight against obesity.
Topics: Adenosine; Adipogenesis; Adipose Tissue; Epigenesis, Genetic; Humans; Methylation; RNA Processing, Post-Transcriptional
PubMed: 32935469
DOI: 10.1111/obr.13124 -
Journal of Cellular Physiology Feb 2019Adipose cells store lipids in the cytoplasm and signal systemically through secretion of adipokines and other molecules that regulate body energy metabolism.... (Review)
Review
Adipose cells store lipids in the cytoplasm and signal systemically through secretion of adipokines and other molecules that regulate body energy metabolism. Differentiation of fat cells and its regulation has been the focus of extensive research since the early 1970s. In this review, we had attempted to examine the research bearing on the control of adipose cell differentiation, some of it dating back to the early days when Howard Green and his group described the preadipocyte cell lines 3T3-L1 and 3T3-F442A during 1974-1975. We also concentrated our attention on research published during the last few years, emphasizing data described on transcription factors that regulate adipose differentiation, outside of those that were reported earlier as part of the canonical adipogenic transcriptional cascade, which has been the subject of ample reviews by several groups of researchers. We focused on the studies carried out with the two preadipocyte cell culture models, the 3T3-L1 and 3T3-F442A cells that have provided essential data on adipose biology.
Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Humans; Mice; Signal Transduction; Transcription Factors; Transcription, Genetic
PubMed: 30146705
DOI: 10.1002/jcp.27060 -
Stem Cell Reviews and Reports Feb 2018Adipogenesis is a complex process whereby the multipotent adipose-derived stem cell is converted to a preadipocyte before terminal differentiation into the mature... (Review)
Review
Adipogenesis is a complex process whereby the multipotent adipose-derived stem cell is converted to a preadipocyte before terminal differentiation into the mature adipocyte. Preadipocytes are present throughout adult life, exhibit adipose fat depot specificity, and differentiate and proliferate from distinct progenitor cells. The mechanisms that promote preadipocyte commitment and maturation involve numerous protein factor regulators, epigenetic factors, and miRNAs. Detailed characterization of this process is currently an area of intense research and understanding the roles of preadipocytes in tissue plasticity may provide insight into novel approaches for tissue engineering, regenerative medicine and treating a host of obesity-related conditions. In the current study, we analyzed the current literature and present a review of the characteristics of transitioning adipocytes and detail how local microenvironments influence their progression towards terminal differentiation and maturation. Specifically, we detail the characterization of preadipocyte via surface markers, examine the signaling cascades and regulation behind adipogenesis and cell maturation, and survey their role in tissue plasticity and health and disease.
Topics: Adipocytes; Adipogenesis; Animals; Cell Differentiation; Humans; Signal Transduction; Stem Cells
PubMed: 29027120
DOI: 10.1007/s12015-017-9774-9 -
ELife Mar 2023In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal bone growth and ossification...
In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche.
Topics: Mice; Animals; Bone Marrow; Glycosylation; Osteogenesis; Cell Differentiation; Adipogenesis; Bone Marrow Cells; Mammals
PubMed: 36861967
DOI: 10.7554/eLife.85464 -
Obesity (Silver Spring, Md.) Dec 2021The rising prevalence of obesity over the past decades coincides with the rising awareness that a detailed understanding of both adipose tissue biology and... (Review)
Review
The rising prevalence of obesity over the past decades coincides with the rising awareness that a detailed understanding of both adipose tissue biology and obesity-associated remodeling is crucial for developing therapeutic and preventive strategies. Substantial progress has been made in identifying the signaling pathways and transcriptional networks that orchestrate alterations of adipocyte gene expression linked to diverse phenotypes. Owing to recent advances in epigenomics, we also gained a better appreciation for the fact that different environmental cues can epigenetically reprogram adipocyte fate and function, mainly by altering DNA methylation and histone modification patterns. Intriguingly, it appears that transcription factors and chromatin-modifying coregulator complexes are the key regulatory components that coordinate both signaling-induced transcriptional and epigenetic alterations in adipocytes. In this review, we summarize and discuss current molecular insights into how these alterations and the involved regulatory components trigger adipogenesis and adipose tissue remodeling in response to energy surplus.
Topics: Adipocytes; Adipogenesis; Epigenesis, Genetic; Epigenomics; Humans; Obesity
PubMed: 34813171
DOI: 10.1002/oby.23248 -
Hormone and Metabolic Research =... Nov 2014Energy storage and release at times of food excess or fasting are carefully coordinated processes that depend on the appropriate differentiation of mesenchymal stem... (Review)
Review
Energy storage and release at times of food excess or fasting are carefully coordinated processes that depend on the appropriate differentiation of mesenchymal stem cells into mature adipocytes (adipogenesis) forming white adipose tissue (WAT) and on regulatory signals for storage (lipogenesis) or mobilization (lipolysis) of triacylglycerides (TAGs) from lipid droplets. It is widely recognized that cAMP signaling via protein kinase A (PKA) is important both in adipogenesis and for hormonal control and lipolysis in WAT. A kinase anchoring proteins (AKAPs) target PKA to distinct subcellular compartments in close proximity to its specific substrates thereby providing spatial and temporal specificity in the mediation of biological effects controlled by the cAMP-PKA pathway. This review will provide an updated overview of some of the sites of regulation by cAMP in adipogenesis and lipolysis and the involvement of AKAPs and highlighting, as a recent example, the AKAP Optical Atrophy 1 (OPA1) and its role in the phosphorylation of Perilipin to induce lipolysis.
Topics: Adipogenesis; Animals; Cell Compartmentation; Cyclic AMP; Humans; Lipogenesis; Lipolysis; Signal Transduction
PubMed: 25247872
DOI: 10.1055/s-0034-1389955 -
PloS One 2022We previously showed that some adipogenic transcription factors such as CEBPB and PPARG directly and indirectly regulate autophagy gene expression in adipogenesis. The...
We previously showed that some adipogenic transcription factors such as CEBPB and PPARG directly and indirectly regulate autophagy gene expression in adipogenesis. The order and effect of these events are undetermined. In this study, we modeled the gene expression, DNA-binding of transcriptional regulators, and histone modifications during adipocyte differentiation and evaluated the effect of the regulators on gene expression in terms of direction and magnitude. Then, we identified the overlap of the transcription factors and co-factors binding sites and targets. Finally, we built a chromatin state model based on the histone marks and studied their relation to the factors' binding. Adipogenic factors differentially regulated autophagy genes as part of the differentiation program. Co-regulators associated with specific transcription factors and preceded them to the regulatory regions. Transcription factors differed in the binding time and location, and their effect on expression was either localized or long-lasting. Adipogenic factors disproportionately targeted genes coding for autophagy-specific transcription factors. In sum, a hierarchical arrangement between adipogenic transcription factors and co-factors drives the regulation of autophagy during adipocyte differentiation.
Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Autophagy; Cell Differentiation; Cell Line; Computational Biology; Gene Expression Regulation; Mice
PubMed: 35081114
DOI: 10.1371/journal.pone.0250865 -
Bone Dec 2020Bone mesenchymal stem cells (BMSCs) are progenitor cells isolated from bone marrow, which keep potential to differentiate into several kinds of cells including... (Review)
Review
Bone mesenchymal stem cells (BMSCs) are progenitor cells isolated from bone marrow, which keep potential to differentiate into several kinds of cells including osteoblasts and adipocytes. A dynamic mutual regulation exists between osteogenesis and adipogenesis processes. Long non-coding RNA (lncRNA) performs diverse functions in biological activities including regulation of BMSCs commitment. Evidence has shown that lncRNA regulates key signaling pathways including TGFβ/BMP, Wnt and Notch pathways, and several transcription factors in BMSCs differention. Dysregulation of lncRNA in BMSCs leads to disruption of osteo-adipogenesis difffrentiation and results in impairment of bone homeostasis. In this review, we focus on the role of lncRNA in several critical signaling pathways that involved in regulation of osteo-adipogenesis of BMSC and prospects the potential clinical application of lncRNA.
Topics: Adipogenesis; Bone Marrow Cells; Cell Differentiation; Mesenchymal Stem Cells; Osteoblasts; Osteogenesis; RNA, Long Noncoding
PubMed: 32853852
DOI: 10.1016/j.bone.2020.115617 -
Annals of Medicine Mar 2015Evidence from rodents established an important role of brown adipose tissue (BAT) in energy expenditure. Moreover, to sustain thermogenesis, BAT has been shown to be a... (Review)
Review
Evidence from rodents established an important role of brown adipose tissue (BAT) in energy expenditure. Moreover, to sustain thermogenesis, BAT has been shown to be a powerful sink for draining and oxidation of glucose and triglycerides from blood. The potential of BAT activity in protection against obesity and metabolic syndrome is recognized. Recently, an unexpected presence and activity of BAT has been found in adult humans. Here we review the most recent research in this field and, specifically, how new findings apply to humans. Moreover, we seek to clarify the underlying biological processes occurring beyond the burst of new nomenclature in the field. The cell type responsible for thermogenesis, the brown adipocyte, arises from complex developmental processes. In addition to 'classical' brown adipocytes, present in developmentally programmed BAT depots, there are brown adipocytes, named 'brite' (from 'brown-in-white') or 'beige', which appear in response to thermogenic stimuli in white fat due to the so-called 'browning' process. Beige/brite cells appear to be important components of BAT depots in adult humans. In addition to the known control of BAT activity by the sympathetic nervous system, metabolic and hormonal signals originating in muscle or liver (e.g. irisin, FGF21) are recognized as activators of BAT and beige/brite adipocytes.
Topics: Adipocytes, Brown; Adipogenesis; Adipose Tissue, Brown; Animals; Energy Metabolism; Humans; Obesity; Thermogenesis
PubMed: 25230914
DOI: 10.3109/07853890.2014.952328