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Book ; Online: Bone Marrow Adipose Tissue: Formation; Function; and Impact on Health and Disease

Scheller, Erica L. / Cawthorn, William P.

2017

Abstract: Adipocytes are a major component of the bone marrow, accounting for up to 70% of total bone marrow volume in healthy humans. Indeed, this bone marrow adipose tissue (often referred to as 'MAT' or 'BMAT') accounts for at least 5% of total adipose tissue ... ...

Abstract	Adipocytes are a major component of the bone marrow, accounting for up to 70% of total bone marrow volume in healthy humans. Indeed, this bone marrow adipose tissue (often referred to as 'MAT' or 'BMAT') accounts for at least 5% of total adipose tissue mass in lean, healthy humans, suggesting a role in normal physiology and development. Bone marrow adiposity further increases with ageing and in diverse clinical conditions, including major public health challenges such as osteoporosis. Yet despite this abundance and compelling clinical potential, bone marrow adipocytes have received surprisingly little attention from the biomedical research community. Thankfully, this is now beginning to change. Research over the past decade has begun to increase our knowledge of BMAT, including the conditions associated with altered bone marrow adiposity and the potential physiological and pathological functions of bone marrow adipocytes. The articles within this e-Book highlight many of these recent developments, underscoring our increasing knowledge of BMAT formation and function; showcasing emerging techniques for basic and clinical BMAT analysis; and highlighting key questions and future directions for this burgeoning and increasingly diverse field. The editors would like to express their thanks to the authors for contributing the articles within this e-Book; to the senior editors at Frontiers in Endocrinology for their guidance; and to the staff at Frontiers for their helpful input throughout
Keywords	Medicine (General) ; Diseases of the endocrine glands. Clinical endocrinology
Size	1 electronic resource (165 p.)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020097389
ISBN	9782889452453 ; 288945245X
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Turning the spotlight on bone marrow adipocytes in haematological malignancy and non-malignant conditions.

Austin, Michael J / Kalampalika, Foteini / Cawthorn, William P / Patel, Bela

British journal of haematology

2023 Volume 201, Issue 4, Page(s) 605–619

Abstract: Whilst bone marrow adipocytes (BMAd) have long been appreciated by clinical haemato-pathologists, it is only relatively recently, in the face of emerging data, that the adipocytic niche has come under the watchful eye of biologists. There is now mounting ...

Abstract	Whilst bone marrow adipocytes (BMAd) have long been appreciated by clinical haemato-pathologists, it is only relatively recently, in the face of emerging data, that the adipocytic niche has come under the watchful eye of biologists. There is now mounting evidence to suggest that BMAds are not just a simple structural entity of bone marrow microenvironments but a bona fide driver of physio- and pathophysiological processes relevant to multiple aspects of health and disease. Whilst the truly multifaceted nature of BMAds has only just begun to emerge, paradigms have shifted already for normal, malignant and non-malignant haemopoiesis incorporating a view of adipocyte regulation. Major efforts are ongoing, to delineate the routes by which BMAds participate in health and disease with a final aim of achieving clinical tractability. This review summarises the emerging role of BMAds across the spectrum of normal and pathological haematological conditions with a particular focus on its impact on cancer therapy.
MeSH term(s)	Humans ; Bone Marrow/pathology ; Hematologic Neoplasms/therapy ; Hematologic Neoplasms/pathology ; Hematologic Diseases/therapy ; Hematologic Diseases/pathology ; Adipocytes/pathology ; Tumor Microenvironment
Language	English
Publishing date	2023-04-17
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18748
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Article ; Online: Fat cell progenitors get singled out.

Chau, You-Ying / Cawthorn, William P

Science (New York, N.Y.)

2019 Volume 364, Issue 6438, Page(s) 328–329

MeSH term(s)	Adipocytes ; Adipose Tissue ; Mesenchymal Stem Cells ; Stem Cells
Language	English
Publishing date	2019-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aax2967
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Article: Molecular Interaction of Bone Marrow Adipose Tissue with Energy Metabolism.

Suchacki, Karla J / Cawthorn, William P

Current molecular biology reports

2018 Volume 4, Issue 2, Page(s) 41–49

Abstract: Purpose of review: The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT ... ...

Abstract	Purpose of review: The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT. Recent findings: Though still dwarfed by research into white and brown adipose tissues, BMAT is now recognised as endocrine organ and is attracting increasing attention from biomedical researchers around the globe. Summary: We are beginning to learn the importance of BMAT both within and beyond the bone, allowing us to better appreciate the role of BMAT in normal physiology and disease.
Language	English
Publishing date	2018-04-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2198-6428
ISSN	2198-6428
DOI	10.1007/s40610-018-0096-8
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Article: Editorial: Bone Marrow Adipose Tissue: Formation, Function, and Impact on Health and Disease.

Cawthorn, William P / Scheller, Erica L

Frontiers in endocrinology

2017 Volume 8, Page(s) 112

Language	English
Publishing date	2017-05-29
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2017.00112
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Article ; Online: Bone marrow adipose tissue as an endocrine organ: close to the bone?

Sulston, Richard J / Cawthorn, William P

Hormone molecular biology and clinical investigation

2016 Volume 28, Issue 1, Page(s) 21–38

Abstract: White adipose tissue (WAT) is a major endocrine organ, secreting a diverse range of hormones, lipid species, cytokines and other factors to exert diverse local and systemic effects. These secreted products, known as 'adipokines', contribute extensively ... ...

Abstract	White adipose tissue (WAT) is a major endocrine organ, secreting a diverse range of hormones, lipid species, cytokines and other factors to exert diverse local and systemic effects. These secreted products, known as 'adipokines', contribute extensively to WAT's impact on physiology and disease. Adipocytes also exist in the bone marrow (BM), but unlike WAT, study of this bone marrow adipose tissue (MAT) has been relatively limited. We recently discovered that MAT contributes to circulating adiponectin, an adipokine that mediates cardiometabolic benefits. Moreover, we found that MAT expansion exerts systemic effects. Together, these observations identify MAT as an endocrine organ. Additional studies are revealing further secretory functions of MAT, including production of other adipokines, cytokines and lipids that exert local effects within bone. These observations suggest that, like WAT, MAT has secretory functions with diverse potential effects, both locally and systemically. A major limitation is that these findings are often based on in vitro approaches that may not faithfully recapitulate the characteristics and functions of BM adipocytes in vivo. This underscores the need to develop improved methods for in vivo analysis of MAT function, including more robust transgenic models for MAT targeting, and continued development of techniques for non-invasive analysis of MAT quantity and quality in humans. Although many aspects of MAT formation and function remain poorly understood, MAT is now attracting increasing research focus; hence, there is much promise for further advances in our understanding of MAT as an endocrine organ, and how MAT impacts human health and disease.
MeSH term(s)	Adipose Tissue/physiology ; Animals ; Bone Marrow/physiology ; Endocrine System/physiology ; Humans
Language	English
Publishing date	2016-10-01
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2536635-X
ISSN	1868-1891 ; 1868-1883
ISSN (online)	1868-1891
ISSN	1868-1883
DOI	10.1515/hmbci-2016-0012
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Article: A novel deep learning method for large-scale analysis of bone marrow adiposity using UK Biobank Dixon MRI data.

Morris, David M / Wang, Chengjia / Papanastasiou, Giorgos / Gray, Calum D / Xu, Wei / Sjöström, Samuel / Badr, Sammy / Paccou, Julien / Semple, Scott Ik / MacGillivray, Tom / Cawthorn, William P

Computational and structural biotechnology journal

2023 Volume 24, Page(s) 89–104

Abstract: Background: Bone marrow adipose tissue (BMAT) represents > 10% fat mass in healthy humans and can be measured by magnetic resonance imaging (MRI) as the bone marrow fat fraction (BMFF). Human MRI studies have identified several diseases associated with ... ...

Abstract	Background: Bone marrow adipose tissue (BMAT) represents > 10% fat mass in healthy humans and can be measured by magnetic resonance imaging (MRI) as the bone marrow fat fraction (BMFF). Human MRI studies have identified several diseases associated with BMFF but have been relatively small scale. Population-scale studies therefore have huge potential to reveal BMAT's true clinical relevance. The UK Biobank (UKBB) is undertaking MRI of 100,000 participants, providing the ideal opportunity for such advances. Objective: To establish deep learning for high-throughput multi-site BMFF analysis from UKBB MRI data. Materials and methods: We studied males and females aged 60-69. Bone marrow (BM) segmentation was automated using a new lightweight attention-based 3D U-Net convolutional neural network that improved segmentation of small structures from large volumetric data. Using manual segmentations from 61-64 subjects, the models were trained to segment four BM regions of interest: the spine (thoracic and lumbar vertebrae), femoral head, total hip and femoral diaphysis. Models were tested using a further 10-12 datasets per region and validated using datasets from 729 UKBB participants. BMFF was then quantified and pathophysiological characteristics assessed, including site- and sex-dependent differences and the relationships with age, BMI, bone mineral density, peripheral adiposity, and osteoporosis. Results: Model accuracy matched or exceeded that for conventional U-Nets, yielding Dice scores of 91.2% (spine), 94.5% (femoral head), 91.2% (total hip) and 86.6% (femoral diaphysis). One case of severe scoliosis prevented segmentation of the spine, while one case of Non-Hodgkin Lymphoma prevented segmentation of the spine, femoral head and total hip because of T2 signal depletion; however, successful segmentation was not disrupted by any other pathophysiological variables. The resulting BMFF measurements confirmed expected relationships between BMFF and age, sex and bone density, and identified new site- and sex-specific characteristics. Conclusions: We have established a new deep learning method for accurate segmentation of small structures from large volumetric data, allowing high-throughput multi-site BMFF measurement in the UKBB. Our findings reveal new pathophysiological insights, highlighting the potential of BMFF as a novel clinical biomarker. Applying our method across the full UKBB cohort will help to reveal the impact of BMAT on human health and disease.
Language	English
Publishing date	2023-12-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2023.12.029
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Article ; Online: Bone marrow adipose tissue: formation, function and regulation.

Suchacki, Karla J / Cawthorn, William P / Rosen, Clifford J

Current opinion in pharmacology

2016 Volume 28, Page(s) 50–56

Abstract: The human body requires an uninterrupted supply of energy to maintain metabolic homeostasis and energy balance. To sustain energy balance, excess consumed calories are stored as glycogen, triglycerides and protein, allowing the body to continue to ... ...

Abstract	The human body requires an uninterrupted supply of energy to maintain metabolic homeostasis and energy balance. To sustain energy balance, excess consumed calories are stored as glycogen, triglycerides and protein, allowing the body to continue to function in states of starvation and increased energy expenditure. Adipose tissue provides the largest natural store of excess calories as triglycerides and plays an important role as an endocrine organ in energy homeostasis and beyond. This short review is intended to detail the current knowledge of the formation and role of bone marrow adipose tissue (MAT), a largely ignored adipose depot, focussing on the role of MAT as an endocrine organ and highlighting the pharmacological agents that regulate MAT.
MeSH term(s)	Adipose Tissue/drug effects ; Adipose Tissue/metabolism ; Animals ; Bone Marrow/drug effects ; Bone Marrow/metabolism ; Energy Intake/physiology ; Energy Metabolism/physiology ; Glycogen/metabolism ; Homeostasis/physiology ; Humans ; Proteins/metabolism ; Triglycerides/metabolism
Chemical Substances	Proteins ; Triglycerides ; Glycogen (9005-79-2)
Language	English
Publishing date	2016-03-26
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2016.03.001
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Article: New Insights Into the Long Non-coding RNA SRA: Physiological Functions and Mechanisms of Action.

Sheng, Liang / Ye, Lan / Zhang, Dong / Cawthorn, William P / Xu, Bin

Frontiers in medicine

2018 Volume 5, Page(s) 244

Abstract: Long non-coding RNAs (lncRNA) are emerging as new genetic/epigenetic regulators that can impact almost all physiological functions. Here, we focus on the long non-coding steroid receptor RNA activator (SRA), including new insights into its effects on ... ...

Abstract	Long non-coding RNAs (lncRNA) are emerging as new genetic/epigenetic regulators that can impact almost all physiological functions. Here, we focus on the long non-coding steroid receptor RNA activator (SRA), including new insights into its effects on gene expression, the cell cycle, and differentiation; how these relate to physiology and disease; and the mechanisms underlying these effects. We discuss how SRA acts as an RNA coactivator in nuclear receptor signaling; its effects on steroidogenesis, adipogenesis, and myocyte differentiation; the impact on breast and prostate cancer tumorigenesis; and, finally, its ability to modulate hepatic steatosis through several signaling pathways. Genome-wide analysis reveals that SRA regulates hundreds of target genes in adipocytes and breast cancer cells and binds to thousands of genomic sites in human pluripotent stem cells. Recent studies indicate that SRA acts as a molecular scaffold and forms networks with numerous coregulators and chromatin-modifying regulators in both activating and repressive complexes. We discuss how modifications to SRA's unique stem-loop secondary structure are important for SRA function, and highlight the various SRA isoforms and mutations that have clinical implications. Finally, we discuss the future directions for better understanding the molecular mechanisms of SRA action and how this might lead to new diagnostic and therapeutic approaches.
Language	English
Publishing date	2018-09-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2018.00244
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Article ; Online: The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent.

eLife

2023 Volume 12

Abstract: Caloric restriction (CR) reduces the risk of age-related diseases in numerous species, including humans. CR's metabolic effects, including decreased adiposity and improved insulin sensitivity, are important for its broader health benefits; however, the ... ...

Abstract	Caloric restriction (CR) reduces the risk of age-related diseases in numerous species, including humans. CR's metabolic effects, including decreased adiposity and improved insulin sensitivity, are important for its broader health benefits; however, the extent and basis of sex differences in CR's health benefits are unknown. We found that 30% CR in young (3-month-old) male mice decreased fat mass and improved glucose tolerance and insulin sensitivity, whereas these effects were blunted or absent in young females. Females' resistance to fat loss was associated with decreased lipolysis, energy expenditure and fatty acid oxidation, and increased postprandial lipogenesis, compared to males. The sex differences in glucose homeostasis were not associated with differential glucose uptake but with altered hepatic ceramide content and substrate metabolism: compared to CR males, CR females had lower TCA cycle activity and higher blood ketone concentrations, a marker of hepatic acetyl-CoA content. This suggests that males use hepatic acetyl-CoA for the TCA cycle whereas in females it accumulates, stimulating gluconeogenesis and limiting hypoglycaemia during CR. In aged mice (18-months old), when females are anoestrus, CR decreased fat mass and improved glucose homeostasis similarly in both sexes. Finally, in a cohort of overweight and obese humans, CR-induced fat loss was also sex- and age-dependent: younger females (<45 years) resisted fat loss compared to younger males while in older subjects (>45 years) this sex difference was absent. Collectively, these studies identify age-dependent sex differences in the metabolic effects of CR and highlight adipose tissue, the liver and oestrogen as key determinants of CR's metabolic benefits. These findings have important implications for understanding the interplay between diet and health, and for maximising the benefits of CR in humans.
MeSH term(s)	Humans ; Male ; Female ; Mice ; Animals ; Aged ; Middle Aged ; Infant ; Caloric Restriction ; Insulin Resistance ; Weight Loss ; Acetyl Coenzyme A ; Adipose Tissue/metabolism ; Obesity ; Glucose/metabolism
Chemical Substances	Acetyl Coenzyme A (72-89-9) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-04-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.88080
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