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Circulating plasma microRNAs dysregulation and metabolic endotoxemia induced by a high-fat high-saturated diet
Bruna Jardim Quintanilha1, Ludmila Rodrigues Pinto Ferreira2, Frederico Moraes Ferreira3
1Nutritional Genomics and Inflammation Laboratory, Department of Nutrition, School of Public Health, University of São Paulo, 01246-904 São Paulo, Brazil; Food Research Center (FoRC), CEPID-FAPESP, Research Innovation and Dissemination Centers São Paulo Research Foundation, São Paulo 05468-140, Brazil.
Abstract:
High-fat diet increase two to three times the plasma lipopolysaccharide (LPS) levels and induce subclinical inflammation. Diet can modify gene expression due to epigenetic processes related to MicroRNAs (miRNAs). MicroRNAs (miRNAs) play important role in the post-transcriptional mechanisms involved in regulation of expression of genes related to the inflammatory response. Also, diet can indirectly induce post-transcriptional regulation of gene expression by miRNAs, which may affect the risk for the development of chronic diseases.
Objective:
This study investigated the effect of high-fat high-saturated meal ingestion on plasma miRNA expression and LPS levels during the postprandial period in healthy women.
Methods:
An interventional study was carried out in which a high-fat breakfast (1067.45 kcal), composed mainly of saturated fatty acids (56 g), and 500 mL of water, was offered. Blood samples were collected at baseline and 1, 3 and 5 h after meal intake. The studied population consisted of healthy women (n = 11), aged between 20 and 40 years, and body mass index (BMI) between 18.5 and 25 kg/m2. Plasma levels of lipid profile, cytokines, adhesion molecules, and LPS were measured at the 3 time points. A profile of 752 human plasma miRNA expression was analyzed by real-time PCR assay. These analyzes were performed for all blood collection time-points.
Results:
Expression profile analysis revealed 33 differentially expressed plasma circulating miRNAs compared to that of the control group. MiR-145-5p and miR-200 were differentially modulated in all time-points post meal consumption. In addition, there was a significant increase in plasma LPS, triglycerides, myristic and palmitic saturated fatty acids levels at the 3 time-points in comparison with the control basal levels. We also observed increased levels of the plasma tumor necrosis factor alpha (TNF-α) cytokine and the vascular cell adhesion molecule 1 (VCAM-1) levels after 5 h post meal ingestion.
Conclusion:
Ingestion of high-fat high-saturated meal was able to induce metabolic endotoxemia and increase the expression of pro-inflammatory molecules such as TNF-alpha and VCAM-1, as well as modulating circulating miRNAs possibly controlling inflammatory and lipid metabolism proteins at the postprandial period.
Insights
A high-fat meal increased lipopolysaccharide (LPS) and inflammatory markers in healthy women, altering circulating microRNA (miRNA) profiles. This suggests diet-induced endotoxemia and inflammation may be regulated by miRNAs post-meal.
Area of Science:
- Nutrition Science
- Molecular Biology
- Immunology
Background:
- High-fat diets elevate plasma lipopolysaccharide (LPS) and induce subclinical inflammation.
- MicroRNAs (miRNAs) are key epigenetic regulators of gene expression, particularly in inflammatory responses.
- Dietary intake can influence gene expression post-transcriptionally via miRNAs, potentially impacting chronic disease risk.
Purpose of the Study:
- To investigate the impact of a high-fat, high-saturated meal on plasma miRNA expression and LPS levels.
- To analyze postprandial changes in inflammatory markers and lipid profiles in healthy women.
Main Methods:
- An interventional study involving 11 healthy women (aged 20-40) who consumed a high-fat breakfast.
- Blood samples collected at baseline and 1, 3, and 5 hours post-meal for analysis of lipids, cytokines, adhesion molecules, LPS, and plasma miRNA expression (752 miRNAs).
Main Results:
- 33 differentially expressed plasma circulating miRNAs were identified post-meal compared to baseline.
- Significant increases in plasma LPS, triglycerides, and specific fatty acids were observed post-meal.
- Elevated levels of tumor necrosis factor alpha (TNF-α) and vascular cell adhesion molecule 1 (VCAM-1) were noted 5 hours after meal ingestion.
Conclusions:
- High-fat, high-saturated meal ingestion induced metabolic endotoxemia and increased pro-inflammatory markers (TNF-α, VCAM-1).
- Circulating miRNA expression was modulated postprandially, suggesting a role in regulating inflammatory and lipid metabolism proteins.
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