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BMI-adjusted adipose tissue volumes exhibit depot-specific and divergent associations with cardiometabolic diseases

Author

Listed:
  • Saaket Agrawal

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Marcus D. R. Klarqvist

    (Broad Institute of MIT and Harvard)

  • Nathaniel Diamant

    (Broad Institute of MIT and Harvard)

  • Takara L. Stanley

    (Massachusetts General Hospital)

  • Patrick T. Ellinor

    (Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Nehal N. Mehta

    (National Institutes of Health)

  • Anthony Philippakis

    (Broad Institute of MIT and Harvard
    Broad Institute of MIT and Harvard)

  • Kenney Ng

    (IBM Research)

  • Melina Claussnitzer

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Steven K. Grinspoon

    (Massachusetts General Hospital)

  • Puneet Batra

    (Broad Institute of MIT and Harvard)

  • Amit V. Khera

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School
    Verve Therapeutics)

Abstract

For any given body mass index (BMI), individuals vary substantially in fat distribution, and this variation may have important implications for cardiometabolic risk. Here, we study disease associations with BMI-independent variation in visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) fat depots in 40,032 individuals of the UK Biobank with body MRI. We apply deep learning models based on two-dimensional body MRI projections to enable near-perfect estimation of fat depot volumes (R2 in heldout dataset = 0.978-0.991 for VAT, ASAT, and GFAT). Next, we derive BMI-adjusted metrics for each fat depot (e.g. VAT adjusted for BMI, VATadjBMI) to quantify local adiposity burden. VATadjBMI is associated with increased risk of type 2 diabetes and coronary artery disease, ASATadjBMI is largely neutral, and GFATadjBMI is associated with reduced risk. These results – describing three metabolically distinct fat depots at scale – clarify the cardiometabolic impact of BMI-independent differences in body fat distribution.

Suggested Citation

  • Saaket Agrawal & Marcus D. R. Klarqvist & Nathaniel Diamant & Takara L. Stanley & Patrick T. Ellinor & Nehal N. Mehta & Anthony Philippakis & Kenney Ng & Melina Claussnitzer & Steven K. Grinspoon & Pu, 2023. "BMI-adjusted adipose tissue volumes exhibit depot-specific and divergent associations with cardiometabolic diseases," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35704-5
    DOI: 10.1038/s41467-022-35704-5
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