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

(OR07-01-25) Adiposity, Metabolomic and Proteomic Signatures, and Liver Health: A Prospective Cohort Study in the UK Biobank

Sunday, June 1, 2025

10:00 AM – 10:12 AM ET

Location: S220 E-G

Emerging Leaders in Nutrition Science Poster Competition

Presenting Author(s)

Longgang Zhao, PhD

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

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

Co-Author(s)

Yun Chen, PhD (she/her/hers)

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

Jun Li

Brigham and Women's Hospital and Harvard Medical School
TT

Tamar Taddei

Yale School of Medicine, United States
XM

Xiaomei Ma

Yale School of Public Health, United States
SM

Shuangge Ma

Yale School of Public Health, United States
Deirdre K. Tobias, ScD (she/her/hers)

Assistant Professor
Harvard T.H. Chan School of Public Health
Boston, Massachusetts, United States
Edward L. Giovannucci, PhD

Professor of Nutrition and Epidemiology
Harvard T.H. Chan School of Public Health
Boston, Massachusetts, United States
HS

Howard D. Sesso, ScD, MPH

Associate Professor
Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Department of Epidemiology, Harvard T.H. Chan School of Public Health
Boston, Massachusetts, United States
JM

JoAnn E. Manson

Brigham and Women’s Hospital and Harvard Medical School, United States
Frank B. Hu, MD, MPH, PhD

Chair, Department of Nutrition Harvard T.H. Chan School of Public Health Fredrick J. Stare Professor of Nutrition and Epidemiology at Harvard T.H. Chan School of Public Health Professor of Medicine, Harvard Medical School and Brigham and Women’s Hospital
Harvard T.H. Chan School of Public Health
Boston, Massachusetts, United States
XZ

Xuehong Zhang

Yale School of Nursing, United States

Objectives: Excess adiposity is a key risk factor for chronic liver disease (CLD), but the underlying metabolomic and proteomic mechanisms are unclear. We evaluated associations of excess adiposity and related metabolomic and proteomic signatures with risk of liver outcomes.

Methods: We analyzed data from 450,412 UK Biobank participants (40-69 years at baseline). Adiposity was assessed by body mass index (BMI) and waist circumference (WC). CLD outcomes (metabolic dysfunction-associated steatotic liver disease [MASLD], cirrhosis, liver cancer, severe liver diseases [SLD, including hepatocellular carcinoma and other severe liver diseases], and CLD death) were ascertained from in-hospital records, cancer and death registries. We derived novel metabolomic (NMR platform, 168 metabolites) and proteomic scores (Olink platform, 1459 proteins) related to BMI or WC using elastic net regression. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals for associations of omic signatures with liver outcomes, adjusting for age, sex, ethnicity, Townsend deprivation index, alcohol drinking, smoking, physical activity, aspirin use, and history of diabetes.

Results: After a median follow-up of 8.9 years, there were 4,077 cases of MASLD, 3,550 of cirrhosis, 755 of liver cancer, 2,253 of SLD, and 331 CLD deaths. Compared to participants with normal BMI (18.5-23.9 kg/m²), obesity (BMI≥30 kg/m²) was positively associated with risk of all adverse liver outcomes. Central obesity showed similar magnitude. The BMI-related metabolomic (96 metabolites) and proteomic (116 proteins) scores were associated with higher risks of MASLD, cirrhosis, liver cancer, and SLD. The WC-related metabolomic (82 metabolites) and proteomic (116 proteins) scores were associated with higher risks of MASLD, liver cancer, and SLD.

Conclusions: General and central obesity and their omic signatures were positively associated with adverse liver outcomes, revealing the molecular perturbations in metabolites and proteins associated with adiposity and liver health, which may inform the etiology and prevention of liver disease.

Funding Sources: Xuehong Zhang is supported by NIH/NCI R21 CA238651, R21 CA252962, R37 CA262299, U01 CA259208, U01 CA272452, American Cancer Society (RSG NEC-130476, PASD-22-1003396).