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Updated: May 12, 2025
Large Scale Non-targeted Metabolomic Profiling of Serum by Ultra Performance Liquid Chromatography-Mass Spectrometry UPLC-MS
Published on: March 14, 2013
Metabolomic and Proteomic Signatures of Ultra-processed Foods Are Positively Associated with Adverse Liver Outcomes
Longgang Zhao1, Yun Chen2, Alyssa Clay-Gilmour3
1Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC; Yale School of Nursing, Orange, CT.
Background:
Higher consumption of ultra-processed foods is associated with increased risk of obesity and type 2 diabetes; however, evidence on liver diseases and the underlying mechanisms remain limited.
Objectives:
This study aimed to evaluate associations between metabolomic and proteomic signatures of ultra-processed food intake and adverse liver outcomes.
Methods:
Data of participants aged 40 to 69 y from the UK Biobank (N = 173,840) were analyzed. Ultra-processed food intake was assessed using multiple 24-h dietary recalls. Plasma metabolites were measured using nuclear magnetic resonance spectroscopy, and plasma proteome was profiled using the Olink platform. Adverse liver outcomes (metabolic dysfunction-associated steatotic liver disease [MASLD], cirrhosis, liver cancer, and severe liver disease) were ascertained using data from the in-hospital records or cancer or death registries. We used elastic net regression to calculate omics signatures of ultra-processed foods and Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ultra-processed foods and their omics signatures and adverse liver outcomes, adjusting for multiple potential confounding factors.
Results:
With a median follow-up of 8.9 years, an increase of 1 standard deviation (SD) in metabolic signature score of ultra-processed foods was associated with increased risk of MASLD (HR: 1.61; 95% CI: 1.38, 1.87). An increase of 1 SD in proteomic signature score of ultra-processed foods was associated with increased risk of MASLD (HR: 1.84; 95% CI: 1.45, 2.35), cirrhosis (HR: 1.49; 95% CI: 1.16, 1.91), and severe liver disease (HR: 1.48; 95% CI: 1.07, 2.03). Thirty-four metabolites and 65 proteins were significantly associated with ultra-processed food intake and were enriched in biological pathways such as lipid metabolism, immune, and inflammatory response. About half of these metabolites and proteins are significantly associated with risk of MASLD and cirrhosis.
Conclusions:
Ultra-processed food intake and its metabolic and proteomic signatures are positively associated with risk of MASLD.
