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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #406793
Research Project: Improving Public Health by Understanding Metabolic and Bio-Behavioral Effects of Following Recommendations in the Dietary Guidelines for Americans

Location: Obesity and Metabolism Research

Title: Specific circulating miRNAs are associated with plasma lipids in a healthy American cohort

Author
item Evans, Levi
item DURBIN-JOHNSON, BLYTHE - University Of California, Davis
item SUTTON, KRISTEN - University Of California, Davis
item YAM, PHOEBE - University Of California, Davis
item BOUZID, YASMINE - University Of California, Davis
item CERVANTES, EDUARDO - University Of California, Davis
item BONNEL, ELLEN - University Of California, Davis
item Stephensen, Charles
item Bennett, Brian

Submitted to: Physiological Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/27/2024
Publication Date: 7/1/2024
Citation: Evans, L.W., Durbin-Johnson, B., Sutton, K.J., Yam, P., Bouzid, Y., Cervantes, E., Bonnel, E., Stephensen, C.B., Bennett, B.J. 2024. Specific circulating miRNAs are associated with plasma lipids in a healthy American cohort. Physiological Genomics. 56(7):492-505. https://doi.org/10.1152/physiolgenomics.00087.2023.
DOI: https://doi.org/10.1152/physiolgenomics.00087.2023

Interpretive Summary: Cardiovascular diseases (CVDs) are the leading cause of death, despite major progress and accomplishments. High cholesterol specifically relating to low-density lipoprotein cholesterol (LDL-c) is a primary risk-factor of CVD development that has been targeted through medicinal and dietary therapies. However, since individual variability in response to such therapies still remains, newly acquired information about the mechanisms involved in LDL-c regulation and in diet-LDL-c relationships are still highly important. Such mechanisms involve biological molecules like microRNA (miRNA). From data derived from the Nutritional Phenotyping Study, we have identified several miRNA that both positively and negatively associated with LDL-c. Furthermore, we uncovered a relationship between the dietary intake of legumes and a miRNA that negatively associated with LDL-c. These results provide direction for future pre-clinical studies which are currently ongoing in our lab.

Technical Abstract: Low-density lipoprotein cholesterol (LDL-c) is both a therapeutic target and a risk factor for cardio-metabolic disease (CMD). MicroRNA (miRNA) have been shown to regulate cholesterol homeostasis, and miRNA in blood circulation have been linked to hypercholesterolemia as well as other pathologies. However, few studies to date have associated miRNA with phenotypes like LDL-c in a healthy population. To this end, using two separate bioinformatic approaches, we analyzed circulating miRNA in relation to LDL-c and other cardiometabolic phenotypes in a 353 person-cohort free from CMD. The first approach found that miR-15b-5p and miR-16-5p were upregulated in individuals with at-risk levels of LDL-c. The second approach identified miRNA clusters, one of which that positively and a second that negatively correlated with LDL-c. Included in the cluster that positively correlated with LDL-c were miR-15b-5p and miR-16-5p as well as other miRNA from the miR-30 and let-7 families. Cross-species analyses suggested that several miRNA that associate with LDL-c are conserved between mice and humans. Finally, we examined the influence of diet on circulating miRNA. Our results robustly linked circulating miRNA with LDL-c suggesting that miRNA could be used as biomarkers for hypercholesterolemia or targets for developing cholesterol-lowering drugs.