| Title: | Genetic Determinants of Fatty Acid Composition in Subcutaneous and Visceral Adipose Tissue |
| Journal: | Obesity |
| Published: | 29 Sep 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41024449/ |
| DOI: | https://doi.org/10.1002/oby.70045 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/oby.70045 |
Publication 19380
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Abstract
OBJECTIVE: Fatty acids in adipose tissue are key structural and metabolic regulators of cardiometabolic health, but the genetic architecture governing depot-specific composition in subcutaneous (SAT) and visceral adipose tissue (VAT) is not well defined.</p>
METHODS: We used MRI-derived estimates of fatty acid composition in SAT and VAT from 33,583 UK Biobank participants to perform genome-wide association studies. Functional annotation, fine mapping, colocalization, and expression QTL analyses were conducted to prioritize likely causal variants and explore mechanisms.</p>
RESULTS: We identified six loci associated with adipose tissue fatty acid composition, including both shared (PKD2L1, INSIG1) and depot-specific associations (LEKR1 and KLF14 for SAT; CDCA2 for VAT). The strongest association, rs603424-G (near PKD2L1), was linked to higher monounsaturated and polyunsaturated fatty acids, lower saturated fatty acids, and increased SCD1 expression in SAT and VAT, suggesting a role in desaturation and lipid remodeling. Several loci were linked to cardiometabolic outcomes including type 2 diabetes, hypertension, and cholelithiasis, with functional evidence supporting gene-diet interactions at the PKD2L1 locus.</p>
CONCLUSIONS: Our findings uncover genetic determinants of human adipose tissue fatty acid composition, highlight depot-specific regulation, and point to SCD1 as a potential metabolic regulator. These results deepen understanding of lipid metabolism and its links to cardiometabolic risk.</p>
9 Authors
- Altayeb Ahmed
- Afreen Naz
- Marjola Thanaj
- Elena P. Sorokin
- Brandon Whitcher
- Jimmy D. Bell
- E. Louise Thomas
- Madeleine Cule
- Hanieh Yaghootkar
1 Application
| Application ID | Title |
|---|---|
| 44584 | Enriched Image Based Phenotypes for Health Exploration and Discovery |
Enabling scientific discoveries that improve human health