Sprinkles, Jessica K.; Qin, Qiyao; Steward, Charles; Howard, Annie Green; Lulla, Anju; Hullings, Autumn G.; Carr, J. Jeffrey; Shaikh, Saame Raza; Avery, Christy L.; North, Kari E.; Gordon-Larsen, Penny; Meyer, Katie A. (2026).听.听PLOS ONE, 21(3), e0341462.听
This study examines how different types of fats and related molecules in the blood are linked to聽metabolic-associated steatotic liver disease (MASLD), a condition where excess fat builds up in the liver. While this buildup mainly involves聽triacylglycerols (TAGs)聽(a common form of fat), other lipids (fat-like molecules) and nutrients鈥攅specially those involved in聽choline metabolism鈥攎ay also play important roles. Choline is a nutrient that helps the liver package and export fats using particles called聽very low-density lipoproteins (VLDL), which carry fat through the bloodstream. However, large population studies that look at these factors together have been limited.
Using data from over 1,000 middle-aged adults in the CARDIA study, the researchers analyzed blood samples to measure a wide range of lipids (lipidomics, the large-scale study of fats in the body) and choline-related compounds. They also assessed liver fat using CT scans. They found that higher levels of certain lipids鈥攕uch as TAGs,聽diacylglycerols (DAGs), and聽dihydroceramides (DCERs)鈥攚ere linked to a greater likelihood of MASLD, while higher levels of聽lactosylceramides (LCERs)聽were linked to a lower likelihood. When looking more closely at聽phosphatidylcholines (PCs)鈥攁 class of lipids important for fat transport鈥攖heir relationship with MASLD depended on the types of fatty acids (FA composition) they contained, suggesting that not all PCs behave the same way in the disease process.
The study also found that聽betaine, a molecule derived from choline, was associated with a lower risk of MASLD. In contrast, a combined 鈥渓ipid risk score鈥� based on multiple lipid types was positively associated with choline levels but negatively associated with betaine. Overall, these findings highlight complex interactions between different fats and choline-related molecules in the development of MASLD. They suggest that both the types of fats and how the body processes choline may influence liver health, offering potential clues for identifying biomarkers (measurable indicators of disease) and better understanding the underlying biology of the condition.
Fig 1.听Multivariable-adjusted associations between lipid classes and metabolic associated steatotic liver disease.
Multivariable-adjusted risk ratios (95% CI) from a Poisson regression model adjusted for race (Black/White), examination center (Birmingham, AL; Chicago, IL; Minneapolis, MN; Oakland, CA), age (continuous), attained education (continuous), sex (male/female), smoking (current/not current), physical activity score (continuous), dietary intake as food groups (continuous), caloric intake (continuous), a priori diet quality score (continuous), eGFR (continuous), BMI (continuous), hypertension (yes/no), and lipid-lowering cholesterol medication use (yes/no). MASLD cases/non-cases鈥�=鈥�219/764; Observations removed due to missing covariate data鈥�=鈥�133.听CE聽cholesteryl ester,聽CER听肠别谤补尘颈诲别,听DAG诲颈补肠测濒驳濒测肠别谤辞濒,听DCER听诲颈丑测诲谤辞肠别谤补尘颈诲别,听HCER听丑别虫辞蝉测濒肠别谤补尘颈诲别,听LCER尝补肠迟辞蝉测濒肠别谤补尘颈诲别,听LPE听濒测蝉辞辫丑辞蝉辫丑补迟颈诲测濒肠丑辞濒颈苍别,听MAG听尘辞苍辞补肠测濒驳濒测肠别谤辞濒,听PC辫丑辞蝉辫丑补迟颈诲测濒肠丑辞濒颈苍别,听PE听辫丑辞蝉辫丑补迟颈诲测濒别迟丑补苍辞濒补尘颈苍别,听PI听辫丑辞蝉辫丑补迟颈诲测濒颈苍辞蝉颈迟辞濒,听SM蝉辫丑颈苍驳辞尘测别濒颈苍,听TAG听迟谤颈补肠测濒驳濒测肠别谤辞濒.