Obesity, Precision Nutrition, and Body Composition (Oral Session 7)

(OR07-07-25) Cumulative Lipids Exposure Through Young Adulthood and Metabolic Dysfunction-Associated Steatotic Liver Disease in Midlife

Sunday, June 1, 2025

11:12 AM – 11:24 AM ET

Location: S220 E-G

Presenting Author(s)

Yun Chen, PhD (she/her/hers)

Postdoctoral Associate
Yale School of Nursing
New Haven, Connecticut, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

YZ

Yinan Zheng

Northwestern University
Longgang Zhao, PhD

Postdoctoral Associate
Yale School of Nursing
Orange, Connecticut, United States
TG

Tao Gao

Northwestern University Feinberg School of Medicine, United States
YQ

Yishu Qu

Northwestern University Feinberg School of Medicine, United States
JC

John Jeffrey Carr

Vanderbilt University School of Medicine, United States
JT

James G. Terry

Vanderbilt University School of Medicine, United States
HN

Hongyan Ning

Northwestern University Feinberg School of Medicine, United States
KK

Kyeezu Kim

Sungkyunkwan University School of Medicine, Republic of Korea
ML

Michelle T. Long, MD, MSc

Clinical Drug Development, Medicine and Science, NASH, Novo Nordisk, Bagsværd, Denmark & Department of Medicine, Section of Gastroenterology, Boston University School of Medicine
Xinyuan Zhang, PhD

Postdoctoral Fellow
Brigham and Women's Hospital and Harvard Medical School
Boston, Massachusetts, United States
JW

John T. Wilkins

Northwestern University Feinberg School of Medicine, United States
AC

Aimin Chen

University of Pennsylvania, United States
KZ

Kai Zhang

University of North Texas Health Science Center at Fort Worth, United States
NA

Norrina Allen

Northwestern University, United States
DL

Donald M. Lloyd-Jones

Northwestern University Feinberg School of Medicine, United States
LH

Lifang Hou

Northwestern University
XZ

Xuehong Zhang

Yale School of Nursing, United States

Objectives: Dyslipidemia is a major modifiable risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), with most evidence focusing on lipid levels measured once in middle or older age. The importance of achieving and maintaining optimal lipid levels across the decades of young adulthood (ages 18-39 years) to prevent MASLD is unclear. We aim to evaluate associations of lipid profiles through young adulthood with midlife MASLD risk and assess mediating effect of epigenomic biomarkers.

Methods: This study included 2577 participants from the Coronary Artery Risk Development in Young Adults (CARDIA), a prospective study. We used data from baseline (Year 0 [Y0], 1985-1986, mean age of 25 years) through 25 years of follow-up (Y25, 2010-2011). We estimated time-weight average (TWA) plasma lipids exposures through young adulthood using up to seven measurements (Y0-Y20). Blood DNA methylation ( >840,000 sites) was measured at Y20. Steatosis at Y25 was measured using non-contrast abdominal computed tomography scans. Logistic regressions were used to quantify associations between TWA lipids and MASLD risk.

Results: 492 MASLD cases were identified. Compared with optimal TWA lipid levels, multivariable-adjusted odds ratios of developing MASLD were 3.26 [95% CI: 2.51-4.25] for abnormal triglycerides (≥100 vs. < 75mg/dL), 2.39 [1.73-3.31] for high-density lipoprotein cholesterol ( < 40[men]/50[women] vs. ≥60mg/dL), 1.77 [1.37-2.30] for non-high-density lipoprotein cholesterol (≥150 vs. < 130mg/dL), 1.74 [1.19-2.51] for apolipoprotein B (≥110 vs. < 90mg/dL), 1.43 [1.08-1.90] for low-density lipoprotein cholesterol (≥130 vs. < 100mg/dL), and 1.39 [1.07-1.81] for total cholesterol (≥200 vs. < 180mg/dL). These associations were consistent across sex, race, and genetic susceptibility of MASLD. DNA methylation markers located in genes CPT1A, ABCG1, and DHCR24 mediated 2.9%-15.4% of observed associations.

Conclusions: Cumulative exposure to abnormal lipids through young adulthood contributes to MASLD development in midlife, partially mediated by lipid-associated DNA methylation. Reducing elevated lipids in early life may lower lifetime MASLD risk, highlighting epigenomic markers’ role in elucidating biological pathways.

Funding Sources: The CARDIA is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI).