Dynamics of Fat Cell Turnover in Humans

Spalding, Kirsty L.; Arner, Peter; Westermark, Pål O.; Bernard, Samuel; Buchholz, Bruce A.; Bergmann, Olaf; Blomqvist, Lennart; Hoffstedt, Johan; Näslund, Erik; Britton, Tom; Concha, Hérnan; Hassan, Moustapha; Rydén, Mikael; Frisén, Jonas

doi:10.1097/01.ogx.0000325910.81966.ac

Cited by 319 publications

(442 citation statements)

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“…An increase in protein synthesis during early chronological aging in ASCs may support ASC homeostasis to satisfy an age‐related increased demand for adipocyte and adipose tissue regeneration. Adipocyte regeneration is a dynamic process . The critical pioneering studies examined adipocyte and lipid turnover rate during human life span and elegantly demonstrated that the definitive number of adipocytes is established during childhood and adolescence.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional and Cell Cycle Alterations Mark Aging of Primary Human Adipose-Derived Stem Cells

et al. 2017

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Adult stem cells play a critical role in the maintenance of tissue homeostasis and prevention of aging. While the regenerative potential of stem cells with low cellular turnover, such as adipose-derived stem cells (ASC), is increasingly recognized, the study of chronological aging in ASCs is technically difficult, and remains poorly understood. Here, we employ our model of chronological aging in primary human ASCs to examine genome-wide transcriptional networks. We demonstrate first that the transcriptome of aging ASCs is distinctly more stable than that of age-matched fibroblasts, and further, that age-dependent modifications in cell cycle progression and translation initiation specifically characterize aging ASCs in conjunction with increased nascent protein synthesis and a distinctly shortened G1 phase. Our results reveal novel chronological aging mechanisms in ASCs that are inherently different from differentiated cells, and that may reflect an organismal attempt to meet the increased demands of tissue and organ homeostasis during aging.

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Section: Discussionmentioning

confidence: 99%

Transcriptional and Cell Cycle Alterations Mark Aging of Primary Human Adipose-Derived Stem Cells

et al. 2017

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“…Finally, our transcriptomic screen also revealed pathways related to energy dissipation, and subsequent detailed analyses indeed confirmed the miR‐26 family to promote brown adipocyte characteristics during adipocyte differentiation. It should be noted that, in humans, there is a constant and substantial turnover of adipocytes throughout adult life which is similar for normal weight and obese individuals . Hence, the ability of the miR‐26 family to drive brite adipogenesis might be of clinical relevance with respect to weight loss.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-26 Family Is Required for Human Adipogenesis and Drives Characteristics of Brown Adipocytes

et al. 2014

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Adipose tissue contains thermogenic adipocytes (i.e., brown and brite/beige) that oxidize nutrients at exceptionally high rates via nonshivering thermogenesis. Its recent discovery in adult humans has opened up new avenues to fight obesity and related disorders such as diabetes. Here, we identified miR-26a and -26b as key regulators of human white and brite adipocyte differentiation. Both microRNAs are upregulated in early adipogenesis, and their inhibition prevented lipid accumulation while their overexpression accelerated it. Intriguingly, miR-26a significantly induced pathways related to energy dissipation, shifted mitochondrial morphology toward that seen in brown adipocytes, and promoted uncoupled respiration by markedly increasing the hallmark protein of brown fat, uncoupling protein 1. By combining in silico target prediction, transcriptomics, and an RNA interference screen, we identified the sheddase ADAM metallopeptidase domain 17 (ADAM17) as a direct target of miR-26 that mediated the observed effects on white and brite adipogenesis. These results point to a novel, critical role for the miR-26 family and its downstream effector ADAM17 in human adipocyte differentiation by promoting characteristics of energy-dissipating thermogenic adipocytes. STEM CELLS 2014;32:1578-1590

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“…Adipose lineage‐committed preadipocytes and stem cells capable of multilineage differentiation (endothelial, adipose, cartilage, and bone) can be isolated from fat stroma [14]. These cells are apparently present throughout life to replace dying adipocytes (in humans approximately 10% of adipocytes are regenerated each year [15]) and for expansion of adipose tissue during times of excess energy availability. However, the identity of these adipocyte progenitors remained unclear because of the heterogeneous population of cells that comprise adipose stroma and absence of markers to distinguish progenitors from other stromal cells.…”

Section: White Adipocyte Progenitors Are Present In Adipose Stromamentioning

confidence: 99%

Concise Review: Adipocyte Origins: Weighing the Possibilities

2011

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Adipose tissue is the primary energy reservoir in the body and an important endocrine organ that plays roles in energy homeostasis, feeding, insulin sensitivity and inflammation. While it was tacitly assumed that fat in different anatomical locations had a common origin and homogenous function, it is now clear that regional differences exist in adipose tissue characteristics and function. This is exemplified by the link between increased deep abdominal or visceral fat, but not peripheral adipose tissue, and the metabolic disturbances associated with obesity. Regional differences in fat function are due in large part to distinct adipocyte populations that comprise the different fat depots. Evidence accrued primarily in the last decade indicate that the distinct adipocyte populations are generated by a number of processes during and after development. These include the production of adipocytes from different germ cell layers, the formation of distinct preadipocyte populations from mesenchymal progenitors of mesodermal origin, and the production of adipocytes from hematopoietic stem cells from the bone marrow. This review will examine each of these process and their relevance to normal adipose tissue formation and contribution to obesity-related diseases.

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Dynamics of Fat Cell Turnover in Humans

Cited by 319 publications

References 0 publications

Transcriptional and Cell Cycle Alterations Mark Aging of Primary Human Adipose-Derived Stem Cells

Transcriptional and Cell Cycle Alterations Mark Aging of Primary Human Adipose-Derived Stem Cells

MicroRNA-26 Family Is Required for Human Adipogenesis and Drives Characteristics of Brown Adipocytes

Concise Review: Adipocyte Origins: Weighing the Possibilities

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