Proteomic signatures may indicate MRI-assessed liver fat

New findings from the DIRECT PLUS, 18-month-long lifestyle intervention trial underscores the potential to observe and signify alterations of MRI-assessed liver fat with proteomics according to new research from Ben-Gurion University of the Negev.

The study was led by Ms. Dana Goldberg, Dr. Anat Yaskolka Meir, and Prof. Iris Shai. An 18-month-long lifestyle intervention trial measured liver fat by MRI and blood proteins for 242 participants at two time points using advanced statistical methods. Their findings were published recently in Hepatology.

Dana Tamar Goldberg, the first author, elaborates on the study findings: "The study results suggest the following: i. Incorporating traditional variables with proteomics may improve liver fat prediction. ii. Three protein changes, CA5A, HAOX1, and THBS2, were independently associated with liver fat relative change, with the green-MED protein change of THBS2 being more prominent than in the MED group after adjusting for weight with liver fat losses. iii. Protein changes over time differed among people with different liver fat percentage groups."

Recent advances in proteomics have deepened insights into Non-alcoholic fatty liver disease (NAFLD), tracing its progression from hepatic steatosis to more severe liver disease such as cirrhosis. NAFLD, often asymptomatic but marked by liver fat accumulation, is associated with broader metabolic and cardiovascular risks. Emerging biomarkers and non-invasive diagnostics are enhancing early detection and staging capabilities.

Prof. Iris Shai, the principal investigator: "The 18-month DIRECT PLUS trial indicated that a green-Mediterranean diet, rich in plant-based proteins and polyphenols and low in red/processed meats, reduced NAFLD by half among the ~300 participants with a NAFLD prevalence of 62% at baseline (PMID:33461965). This diet, which includes Mankai, green tea, and walnuts, also suggested potential benefits for the gut microbiome (PMID:32860791) and epigenetic regulation (PMID:37236302), highlighting its role in the gut-liver axis and hepatic recovery."  

Dr. Anat Yaskolka Meir, a senior member of the research team who was responsible for the liver fat MRI quantification, looks to the future: "Our research advances knowledge on the connection between liver fat percentage and proteomic biomarkers, improving patient monitoring, therapy targeting, personalized treatments, and prognosis evaluation."

Prof. Shai of Ben-Gurion University of the Negev, an adjunct Professor from the Harvard School of Public Health and an honorary professor at the University of Leipzig, Germany, conceived and led the DIRECT PLUS long-term lifestyle intervention trial.

Additional researchers included Ehud Rinott, Alon Kaplan, Gal Tsaban, and Hila Zelicha of BGU, as well as Matthias Blüher, Uta Ceglarek, Michael Stumvoll, Nora Klöting,  Berend Iserman of the University of Leipzig; Ilan Shelef,  Philip Rosen, and Ohad Etzion of Soroka University Medical Center; Meir J. Stampfer and Frank B. Hu of Harvard University.

This work was funded by grants from the German Research Foundation (DFG), German Research Foundation – project number 209933838 – SFB 1052; B11, Israel Ministry of Health grant 87472511; Israel Ministry of Science and Technology grant 3-13604; and the California Walnuts Commission. Dr. Yaskolka Meir is supported by the Council for Higher Education - Zuckerman support program for outstanding postdoctoral female researchers.

None of the funding providers took part in any stage of the design, conduct, or analysis of the study, and they had no access to the study results before publication.

Conflict of interest: Uta Ceglarek received grants from Roche. Matthias Blüher consults, advises, and is on the speakers’ bureau for Lilly. He consults and is on the speakers’ bureau for Amgen, Boehringer-Ingelheim, Novo Nordisk, and Sanofi. He is on the speakers’ bureau for AstraZeneca, Bayer, and Novartis. The remaining authors have no conflicts to report.