Figure 2.

Effects of a High-Fat Diet and a Mediterranean Diet on Dyslipidemia and Atherosclerosis. (A) The High-Fat Diet is composed of large quantities of animal proteins, saturated fats and sugars with decreased fibers and phenols. HFD feeding increase Gram-negative bacteria Ruminococcus and Escherichia spp. while intestinal tight junction proteins occludin and claudin and microbial diversity are reduced. This leads to increased gut permeability, LPS enters the blood stream, resulting in metabolic endotoxemia. Lipopolysaccharides bind TLR-4 on circulating host cells to increase pro-inflammatory cytokines, increased inflammation and reactive oxygen species. Oxidized LDL builds up, causing plaques and increased risk of atherosclerosis. (B) The Mediterranean diet is rich in fibers and phenols, plant-based products, and omega-3 poly-unsaturated fatty acids. The MD increase Clostridium leptum and key genera Faecalibacterium, Lactobacillus, Dialister, Bacteroides, Dialister, Bacteroides and Blautia. It increases SCFA, while upregulating cholesterol and bile acid metabolism by increasing PPAR, CPT-1, FXR activity and decreasing SREBP-1 and FAS activity. This lead to decreased TNF-alpha, TLR4 activation, total cholesterol and LDL, increase HDL and supports intestinal barrier integrity. Less LDL builds up, lessening atherosclerosis and CAD risk. Abbreviations: LPS, Lipopolysaccharides; TLR4, Toll-like receptor 4; LDL, Low-density lipoprotein; IL, interleukin; TNF, Tumor necrosis factor; CAD, coronary artery disease; PUFA, poly-unsaturated fatty acids; PPAR, Peroxisome proliferator activated receptor; CPT-1, Carnitine palmitoyl transferase I; SREBP-1, sterol-regulatory element-binding protein 1; FAS, fatty-acid synthase; HDL, High-density lipoprotein.