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William Cawthorn

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(Principal Investigator)

Investigating how bone marrow adipose tissue and sex differences impact health and disease

Research Area

Research

My research addresses the interplay between metabolism, immunological function and skeletal health in the context of both fundamental biology and chronic diseases. To do so I combine preclinical animal models, human clinical studies and data science approaches using the UK Biobank. Methods include the development of new biomedical imaging techniques and artificial intelligence to open new avenues for population-level studies. My key research interests are as follows:

A) Bone marrow adipose tissue (BMAT):

My overarching research goal is to determine the function of BMAT and its impact on human health. BMAT comprises >10% of total adipose mass in lean, healthy humans, and further increases in diverse clinical contexts. In striking contrast to white adipose tissue (WAT) and brown adipose tissue (BAT), BMAT accumulates during caloric restriction (CR), a condition that promotes healthy ageing by preventing and treating chronic diseases. Thus, altered BMAT formation and/or function might impact numerous human diseases. However, the physiological and pathological functions of BMAT were previously almost completely unknown.

In 2015 I was awarded an MRC Career Development Award to investigate the metabolic and endocrine functions of BMAT. One barrier to understanding BMAT formation and function has been the inability to measure BMAT on a population-level. To address this, in 2019 I was awarded an MRC Research Grant to develop new deep-learning methods for high-throughput, automated analysis of BMAT in the UK Biobank imaging study. My key achievements are as follows:

  1. Discovered that, during states of caloric restriction (CR), BMAT is a key source of adiponectin, a hormone implicated with improved cardiometabolic health (Cawthorn et al, Cell Metabolism 2014).

  2. Identified glucocorticoids as drivers of BMAT accumulation during CR (Cawthorn et al, Endocrinology 2016 and Lovdel et al, Journal of Endocrinology 2024), highlighting mechanisms through which nutritional status regulates BMAT formation.

  3. Developed new biomedical imaging methods to investigate BMAT function in vivo, both preclinically and in humans. This research, which has yielded new research datasets (GSE138690) and software code (ROCPerPixel), revealed that BMAT has high basal glucose uptake and is metabolically distinct from WAT and BAT; thus, BMAT represents a third major, distinct adipose tissue subtype (Suchacki et al, Nature Communications 2020).

  4. Developed deep learning to automate BMAT analysis from MRI data in the UK Biobank (Morris et al 2024), allowing the first genome-wide association studies (GWAS) and phenome-wide association studies (PheWAS) for BMAT (Xu et al, Nature Communications 2025aXu et al, Nature Communications 2025b). Our GWAS data are available on the Musculoskeletal Knowledge Portal.

In 2017 I worked as key member of an international, multidisciplinary team of researchers to co-found The International Bone Marrow Adiposity Society (BMAS; http://bma-society.org/), of which I served as the inaugural Secretary from 2017-2023. I edited the first special issue on BMAT for Frontiers in Endocrinology; lead the BMAS Nomenclature Working Group, with corresponding authorship on our first BMAS position paper (Bravenboer et al, Frontiers in Endocrinology 2020; and serve on of the BMAS Biobanking Working Group, co-authoring biobanking guidelines for BMAT research (Lucas et al, Frontiers in Endocrinology 2021; Tencerova et al., Bone Reports 2025). I am President of the 9th International Meeting on Bone Marrow Adiposity (BMA2026), to be held in Edinburgh from 10-11 September 2026.

Since 2015 my BMAT research has contributed to >30 peer-reviewed journal articles, >36 invited seminars, >30 conference abstracts, 4 PhD theses and 1 book chapter. In 2025 I was awarded the BMAS-Elsevier 'Best Basic Scientist Prize' by the International Bone Marrow Adiposity Society.

B) Adiponectin function in caloric restriction

My finding that BMAT is a key source of adiponectin raises a key question: what is adiponectin’s function during CR? Thus, another of my major research interests is to elucidate adiponectin’s contribution to the metabolic and immunological benefits of CR. I have pursued this goal through preclinical studies in adiponectin knockout (KO) mice, and through Mendelian Randomisation using the UK Biobank. This has revealed that, unexpectedly, adiponectin KO enhances the metabolic benefits of CR (Sulston PhD Thesis) and alters CR’s immunological effects (Mattiucci PhD thesis). A manuscript reporting these findings was first posted as a preprint on bioRxiv (Ikushima et al, 2025) and is now published in PLoS Biology (Ikushima et al, 2026). Moreover, Mendelian Randomisation revealed that decreased circulating adiponectin may influence immunological function in humans, including the risk of adverse COVID-19 outcomes (unpublished studies in progress).

Since 2015 my adiponectin research has contributed to 12 peer-reviewed publications, 28 invited seminars, >12 conference abstracts, 1 preprint and 2 PhD theses. 

C) Sex differences in the effects of caloric restriction

My BMAT and adiponectin research has identified age-dependent sex differences in the CR response, with young females resisting many of CR’s health benefits. For example, in male mice CR decreases fat mass, improves glucose tolerance and suppresses haematopoiesis, whereas females resist these effects. These differences no longer occur in aged mice, in which CR elicits similar metabolic benefits in both sexes. Notably, my research has revealed similar age-dependent sex differences during CR in humans. These findings are reported in our 2023 eLife paper and available as open datasets (University of Edinburgh DataShare, GSE230402 and GSE330380). Our 2026 study in The Journal of Endocrinology further reveals sex differences in the skeletal effects of CR.

To further investigate the basis and extent of these sex differences I have been awarded two research grants (one as PI, one as Co-Investigator) and am the principal supervisor for a final-year PhD student who is contributing to this research.  Since 2015 this research has contributed to 10 peer-reviewed publications, 26 invited seminars, 3 PhD theses, and >18 abstracts at local, national and international meetings. They are the basis for three ongoing interdisciplinary collaborations.

Open Research and Research Integrity

Finally, I am a strong advocate for open research and research integrity. I chair the Open Science Ambassador group of the League of European Research Universities (LERU) and am also the University of Edinburgh’s Institutional co-Lead for the UK Reproducibility Network (UKRN). Through these roles I have contributed to position papers, preregistrations and online resources relevant to research openness and integrity and co-authored the LERU Position Paper “Next Generation Metrics for Scientific and Scholarly Research in Europe”, published in April 2024. Through these positions I help to advance the University of Edinburgh's progress along its Open Research Roadmap, which will help to improve research culture and reproducibility.

Current and Former Team Members 

Adiponectin exerts sex-dependent effects on lipid, amino acid, and glucose metabolism during caloric restriction. 
Ikushima YM, Chen KC, Sulston RJ, Mattiucci D, Brain EJ, Fung Xin Zi SA, Suchacki KJ, Thomas BJ, Lovdel A, Bennett M, Kobayashi H, Whitfield PD, Takubo K, Baker AH, Morton NM, Semple RK and Cawthorn WP PLoS Biology  2026; 24(6), e3003821.

Caloric restriction exerts site-, sex-, and duration-dependent effects on skeletal structure and bone marrow adiposity. 
Chen KC, Sulston RJ, Suchacki KJ, Ikushima YM, Thomas BJ, Lovdel A, Lafond AJ, Mitchell SE, Speakman JR, Morton NM, Semple RK, and Cawthorn WP J Endocrinol  2026; 269(2), e250391.
*Awarded 'Editor's Choice Award', July 2026.

Clinical implications of bone marrow adiposity identified by phenome-wide association and Mendelian randomization in the UK Biobank. 
Xu W, Mesa-Eguiagaray I, Morris DM, Wang C, Gray CD, Sjöström S, Papanastasiou G, Badr S, Paccou J, Wang L, Li X, Timmers PRHJ, Timofeeva M, Semple SIK, MacGillivray T, Theodoratou E, and Cawthorn WP Nature Communications 2025; 16(1):8332.

Deep learning and genome-wide association meta-analyses of bone marrow adiposity in the UK Biobank.
Xu W, Mesa-Eguiagaray I, Morris DM, Wang C, Gray CD, Sjöström S, Papanastasiou G, Badr S, Paccou J, Li X, Timmers PRHJ, Timofeeva M, Farrington SM, Dunlop MG, Semple SIK, MacGillivray T, Theodoratou E, and Cawthorn WP. Nature Communications 2025; 16(1):99.

A novel deep learning method for large-scale analysis of bone marrow adiposity using UK Biobank Dixon MRI data
Morris DM, Wang C, Papanastasiou G, Gray CD, Xu W, Sjöström S, Badr S, Paccou J, Semple SIK, MacGillivray T and Cawthorn WP. Comput Struct Biotechnol J 2024; 24;89-104.

The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent
Suchacki KJ, Thomas BJ, Ikushima YM, Chen KC, Fyfe C, Tavares AAS, Sulston RJ, Lovdel A, Woodward HJ, Han X, Mattiucci D, Brain EJ, Alcaide-Corral CJ, Kobayashi H, Gray GA, Whitfield PD, Stimson RH, Morton NM, Johnstone AM and Cawthorn WP eLife 2023; 12:e88080. 

Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis
Suchacki KJ, Tavares AAS, Mattiucci D, Scheller EL, Papanastasiou G, Gray C, Sinton MC, Ramage LE, McDougald WA, Lovdel A, Sulston RJ, Thomas BJ, Nicholson BM, Drake AJ, Alcaide-Corral CJ, Said D, Poloni A, Cinti S, Macpherson GJ, Dweck MR, Andrews JPM, Williams MC, Wallace RJ, van Beek EJR, MacDougald OA, Morton NM, Stimson RH and Cawthorn WP. Nat. Commun. 2020; 11(1):3097.

Bone marrow adipose tissue
Cawthorn WP. In: Zaidi M, ed. Encyclopedia of Bone Biology. Oxford, UK: Oxford: Academic Press; 2020:156-77 

Open Data, Protocols and Code

  1. Full summary statistics from our BMFF GWASes are available on the Musculoskeletal Knowledge Portal: https://msk.hugeamp.org/downloads.html.

  2. Cawthorn, William. (2026). Dataset: Adiponectin exerts sex-dependent effects on lipid, amino acid, and glucose metabolism during caloric restriction_v2026_05_11, [dataset]. University of Edinburgh. School of Neurological and Cardiovascular Sciences. Institute for Neuroscience and Cardiovascular Research. https://doi.org/10.7488/ds/8126

  3. Cawthorn WP, Ikushima YM, Kobayashi H, Chen K (2026). The effects of adiponectin knockout on hepatic gene expression in male and female C57BL/6NCrl mice fed ad libitum or undergoing caloric restriction. GEO Datasets, GSE330380.

  4. Chen KC and Cawthorn WP (2026). Dataset for Caloric Restriction Timecourse Project. OSF, https://doi.org/10.17605/OSF.IO/CDNU8

  5. Cawthorn WP (2026). Code for analysing data from genome-wide association studies (GWAS) for bone marrow adiposity (BMA). https://github.com/WillCawthorn/BMA_GWAS/, https://doi.org/10.5281/zenodo.18337337

  6. Lovdel A, Homer NZM, Chapman KE, Cawthorn WP (2024). Deletion of Hsd11b1 suppresses caloric-restriction-induced bone marrow adiposity in male but not female mice_v2024_05_07 [dataset]. University of Edinburgh. Edinburgh Medical School. Centre for Cardiovascular Science. https://doi.org/10.7488/ds/7730

  7. Lovdel A, Denham SG, Cawthorn WP, Homer NZM (2024). Extraction and LC-MS/MS analysis of four steroids from mouse plasma and bone marrow. Protocols.io. dx.doi.org/10.17504/protocols.io.e6nvwdrmzlmk/v1

  8. Cawthorn WP, Ikushima YM, Kobayashi H, Chen KC (2023). Sex differences in the effects of caloric restriction (CR) on hepatic gene expression in mice. GEO Datasets, GSE230402

  9. Cawthorn WP, Suchacki, KJ, Thomas, BJ, Ikushima, YM, Chen, KC (2023). The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent, 2003-2023 [dataset]. University of Edinburgh. Edinburgh Medical School. Centre for Cardiovascular Science. https://doi.org/10.7488/ds/3817

  10. Cawthorn WP, Scheller EL, MacDougald OA (2019). Comparison of white adipose tissue and bone marrow adipose tissue from New Zealand White rabbits. GEO Datasets, GSE138690.

  11. Papanastasiou G, Suchacki KJ, Cawthorn WP (2019). ROCPerPixel. GitHub, https://github.com/Georgerun/ROCPerPixel

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    When I'm not engrossed in research I'm usually enjoying time with my family or exploring beautiful Scotland by bike

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    Institute for Neuroscience and Cardiovascular Research

    Queen's Medical Research Institute,

    Edinburgh BioQuarter,

    Edinburgh EH16 4TJ

    University of Edinburgh
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