In a recent study published in Nature Medicine, a group of researchers used lipidomics data to develop a multilipid score (MLS). It reduced MLS (rMLS) to assess the impact of dietary fat quality on lipid metabolites and its association with reduced cardiometabolic disease risk.
Study: Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition. Image Credit: puhhha/Shutterstock.com
Background
Cardiovascular diseases (CVDs) (Disorders of the heart and blood vessels, like heart attack and stroke) cause 20 million global deaths annually, and type 2 diabetes (T2D) (A chronic condition with high blood sugar due to insulin issues) contributes significantly to the noncommunicable disease burden. Reducing CVD and T2D incidence offers substantial societal benefits.
World Health Organization (WHO) and national guidelines recommend reducing saturated fats and increasing unsaturated fats to prevent cardiometabolic diseases. However, the role of dietary fat in cardiometabolic health remains debated, especially regarding high-fat, low-carbohydrate diets (LCDs) versus reducing saturated fats.
The impact of replacing animal-based saturated fats with plant-based unsaturated fats on cardiometabolic risk is unclear. Further research is needed to clarify these effects and understand the genetics, physiology, and diet interplay in lipid metabolism.
About the study
Lipidomics analysis was performed on 113 participants from the 16-week Dietary Intervention and VAScular function (DIVAS) trial, which recruited individuals aged 21 to 60 years with moderate CVD risk. Participants were randomized to one of three isoenergetic diets: rich in saturated fatty acids (SFAs), rich in monounsaturated fatty acids (MUFAs), or rich in mixed unsaturated fatty acids (UFAs).
In the European Prospective Investigation into Cancer and Nutrition - Potsdam (EPIC-Potsdam) cohort, 27,548 participants were recruited to study incident CVD and T2D using a nested case-cohort design.
Anthropometric, blood pressure, and lifestyle data were collected to evaluate disease risk associations. Lipidomics profiling identified lipid markers linked to dietary fat intake and disease outcomes.
The Nurses’ Health Study (NHS) and NHSII cohorts included female nurses who provided blood samples and dietary data over multiple years, with CVD and T2D confirmed through medical records and questionnaires. Lipidomics data were used to construct a rMLS, correlating dietary fat quality with disease risk.
The Prevention with Mediterranean Diet (PREDIMED) trial demonstrated cardiometabolic risk reduction through a Mediterranean diet.
The LIPOGAIN-2 trial focused on overweight individuals assigned to Polyunsaturated fatty acid (PUFA) or SFA-rich diets, monitoring weight and lipid profiles.
Study results
The present study partially validated the DIVAS dietary effects on circulating lipid metabolites in the LIPOGAIN-2 trial, an 8-week overfeeding Randomized Controlled Trial (RCT) with SFA and UFA-enriched diet arms.
Analysis of the NHS and NHSII cohorts and the PREDIMED trial, using Broad Institute lipidomics data, provided relative abundances of a subset of lipid metabolites included in the original MLS.
A rMLS was developed using 42 lower-resolution lipid variables strongly correlating with the original MLS. In the NHS/NHSII cohorts, associations between diet, disease, and 10-year increases in rMLS levels (indicating improved dietary fat quality) were examined, showing a link with reduced T2D risk.
The PREDIMED trial further examined whether individuals with adverse preintervention rMLS levels benefited more from a Mediterranean diet high in plant-based UFAs, particularly nuts and olive oil.
The DIVAS trial involved isoenergetic diets providing 36% of total energy from fats, with a control diet high in SFAs and two intervention arms where 8% of energy from SFAs was replaced with UFAs. Extensive sensitivity analyses showed consistent results across intervention arms.
Participants (n = 113) underwent lipidomics profiling, measuring 987 molecular lipid species concentrations, resulting in 111 lipid class-specific fatty acid concentrations.
The UFA-rich diet significantly reduced circulating concentrations of 45 class-specific fatty acids, particularly those with medium- or long-chain fatty acids with no or few unsaturations.
In the EPIC-Potsdam cohort, the MLS, standardized to the postintervention contrast in the DIVAS trial, was associated with 32% lower CVD and 26% lower T2D incidence.
Adjustments for various biomarkers did not substantially alter these associations, suggesting that the MLS captures the cardiometabolic health impact of altered dietary fat quality more effectively than established surrogate biomarkers.
Replication in the NHS/NHSII cohorts and the LIPOGAIN-2 trial confirmed the MLS associations with diet and disease. The PREDIMED trial showed that a Mediterranean diet reduced T2D risk, particularly in participants with adverse preintervention rMLS levels.
Network analysis in the EPIC-Potsdam cohort identified lipid clusters and direct links between metabolites and disease risk, highlighting the biological processes driving MLS-disease associations.
Conclusions
To summarize, this study found that lipidomics-based MLSs, which reflect the replacement of SFAs with UFAs, were associated with significantly lower risks of CVD and T2D. Analyses from the DIVAS trial and EPIC-Potsdam cohort showed that MLSs predicted greater cardiometabolic risk reductions than standard markers.
Consistent associations between diet, lipid metabolites, and cardiometabolic risk were observed across multiple cohorts.
Additionally, improved lipid scores over ten years were linked to reduced T2D risk, suggesting that lipidomics-based scores can help target dietary interventions for better cardiometabolic health.
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