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

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; Puneet Batra; Amit V Khera

doi:10.1038/s41467-022-35704-5

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

Nat Commun. 2023 Jan 17;14(1):266. doi: 10.1038/s41467-022-35704-5.

Authors

Saaket Agrawal^#^{1

2

3}, Marcus D R Klarqvist^#⁴, Nathaniel Diamant⁴, Takara L Stanley⁵, Patrick T Ellinor^{1

3}, Nehal N Mehta⁶, Anthony Philippakis^{4

7}, Kenney Ng⁸, Melina Claussnitzer^{1

2

3}, Steven K Grinspoon⁵, Puneet Batra⁴, Amit V Khera^{9

10

11

12}

Affiliations

¹ Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
² Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
³ Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁴ Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Metabolism Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁶ National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁷ Eric and Wendy Schmidt Center, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁸ Center for Computational Health, IBM Research, Cambridge, MA, USA.
⁹ Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA. avkhera@mgh.harvard.edu.
¹⁰ Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. avkhera@mgh.harvard.edu.
¹¹ Department of Medicine, Harvard Medical School, Boston, MA, USA. avkhera@mgh.harvard.edu.
¹² Verve Therapeutics, Cambridge, MA, USA. avkhera@mgh.harvard.edu.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adipose Tissue / diagnostic imaging
Adiposity
Body Mass Index
Cardiovascular Diseases* / diagnostic imaging
Cardiovascular Diseases* / metabolism
Diabetes Mellitus, Type 2* / metabolism
Humans
Intra-Abdominal Fat / diagnostic imaging
Intra-Abdominal Fat / metabolism
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding