The impact of supplementation with iso-branched chain fatty acids in a mouse model of atherosclerosis.

BACKGROUND: Serum iso-branched chain fatty acids (iso-BCFAs) levels are inversely correlated with triglyceride and high-sensitivity C-reactive protein (hs-CRP) concentration in obese patients. Moreover, they decrease the expression of genes related to lipogenesis and inflammation in hepatocytes. However, their role in atherosclerosis development remains unclear. This study aimed to assess the impact iso-BCFA supplementation on hyperlipidaemia and inflammation in atherosclerotic apolipoprotein E and low-density lipoprotein receptor double knockout (ApoE-/-/Ldlr⁻/⁻) mice. METHODS: ApoE-/-/Ldlr⁻/⁻ mice were assigned to two experimental groups: (A) fed standard chow (SD-fed) and (B) fed iso-BCFA enriched (BCFA-fed) chow for 12 weeks. Blood samples were collected throughout the study, and tissues were harvested post-mortem. Biochemical analyses were performed using automated assays. FA composition was analyzed by gas chromatography-mass spectrometry (GC-MS). Atherosclerotic plaque area was assessed with Oil Red O staining and vascular inflammation via ecto-adenosine deaminase (eADA) activity. Hepatic gene expression was evaluated via real time PCR. RESULTS: BCFA supplementation led to a stable increase in serum and tissue levels of these FAs. Significant reduction in serum triglyceride and total cholesterol (TC) concentrations was observed in the BCFA-fed group. No change in body weight or serum CRP was detected, whereas the mRNA levels of Il6 in liver were lower after BCFA treatment. However, vascular lipid content and eADA activity were higher in BCFA-fed mice, and hepatic Cpt1 mRNA expression significantly increased, suggesting enhanced β-oxidation. CONCLUSIONS: Dietary iso-BCFA supplementation may modulate lipid metabolism in ApoE-/-/Ldlr⁻/⁻mice. The reduction in triglycerides and TC suggests a potential antiatherosclerosis effects, whereas increased aorta lipid content and eADA activity suggest detrimental effect of BCFA supplementation.