Cumulative lipid exposure in young adulthood and risk of midlife MASLD
Dyslipidemia is a major modifiable risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD). Evidence largely focuses on mid-to-late-life lipid levels, while the impact of cumulative lipid exposure through young adulthood on midlife MASLD risk remains unclear. Using seven repeated lipid measures in a longitudinal observational study, we found that cumulative abnormal lipid exposure during young adulthood (ages 18-39 years) strongly predicted MASLD risk over a 25-year follow-up, outperforming single-visit measures. DNA methylation markers in <i>CPT1A, ABCG1,</i> and <i>DHCR24</i> mediated 2.9%-15.4% of observed associations. Our findings underscore the value of assessing cumulative lipid exposure for midlife MASLD risk stratification and highlight epigenomic mediators as potential targets to strengthen MASLD prevention strategies.
Authors
- J. Jeffrey Carr (ORCID: https://orcid.org/0000-0002-4398-8237)
- Longgang Zhao (ORCID: https://orcid.org/0000-0001-9254-1952)
- Lifang Hou (ORCID: https://orcid.org/0000-0003-4877-0031)
- Hongyan Ning (ORCID: https://orcid.org/0000-0003-1157-6614)
- Donald M. Lloyd‐Jones (ORCID: https://orcid.org/0000-0003-0847-6110)
- John T. Wilkins (ORCID: https://orcid.org/0000-0002-8781-1329)
- Yishu Qu (ORCID: https://orcid.org/0000-0001-5937-3811)
- Norrina B. Allen (ORCID: https://orcid.org/0000-0002-6993-4384)
- Yinan Zheng (ORCID: https://orcid.org/0000-0002-2006-7320)
- James Greg Terry (ORCID: https://orcid.org/0000-0001-6659-3441)
- Michelle T. Long (ORCID: https://orcid.org/0000-0001-6131-3981)
- Kyeezu Kim (ORCID: https://orcid.org/0000-0002-9094-9011)
- Tao Gao (ORCID: https://orcid.org/0000-0002-9462-9349)
- Kai Zhang (ORCID: https://orcid.org/0000-0002-2589-2880)
- Aimin Chen (ORCID: https://orcid.org/0000-0001-9713-6438)
- Xuehong Zhang (ORCID: https://orcid.org/0000-0002-8260-8508)
- Xinyuan Zhang
- Yun Chen (ORCID: https://orcid.org/0009-0001-3783-2199)
Institutions
- Boston University (US)
- Northwestern University (US)
- University of North Texas (US)
- Brigham and Women's Hospital (US)
- Boston Medical Center (US)
- Harvard University (US)
- University of North Texas Health Science Center (US)
- Vanderbilt University (US)
- Yale University (US)
- University of Pennsylvania (US)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- JHEP Reports
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1016/j.jhepr.2025.101679
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00