Impact of fatty acid-enriched diets on cardiac metabolism in young and old mice with gingival infection

Background
Gingival bacterial infection and inflammation have been linked to cardiovascular diseases. Recent studies indicated benefit of immune-modulatory mediterranean-style diets on heart health and periodontal infection and  have shown the benefit of a mediterranean-style diet (MD) in cardiac diseases.However, the exact underlying pathways are unclear and no pathophysiological link between a diet rich in the mono-unsaturated fatty acid oleic acid and cardiac metabolism in the setting of chronic infection and inflammation has been described so far.

Aim of the study was to investigate metabolic changes between different diets in young and old mice with gingival infection status.

Methods
Cardiac tissues were obtained from young (21 weeks) and old (~24 month) C57BL/6J-mice (n=5 per group) fed on oleic acid-enriched (OA-ED) or palmitic acid-ED (PA-ED) or normal standard diet (ND) for 16 weeks undergoing 5 weeks of oral Porphyromonas gingivalis or PBS treatment (placebo), respectively.

Expression of the fatty acid metabolism markers carnitine palmitoyl transferase 1B (CPT1B), PPAR gamma coactivator 1-alpha (PGC1α), pyruvate dehydrogenase kinase 4  (PDK4), fatty acid translocase (CD36) and diacyl glycerol acyltransferase 1 (DGAT1), as well as the expression of glucose transporter 1 (GLUT1) were assessed by quantitative RT-PCR and western blot.

 Results
Western blot analysis revealed a significant increase in cardiac GLUT1 expression in old mice, independent of infection and diet, except in OA-ED placebo mice when compared to young mice (p=0.017 for ND+plac, p=0.0004 for PA+plac, p=0.003 for ND+inf, p=0.007 for OA+inf and p=0.011 for PA+inf, respectively, see Figure). CPT1B expression was increased in old infected mice on OA-ED as compared to placebo mice (p=0.042) and CPT1B and PDK4 expression in young mice were decreased on OA-ED (p=0.048 and p=0.032, respectively). CD36 were found reduced in old infected mice on PA-ED as compared to placebo (p=0.005). Expression of PGC1α was decreased in young infected mice on PA-ED as compared to placebo (p=0.048) as well as in old infected mice on PA-ED and OA-ED (both p=0.049), respectively. DGAT1 shows higher expression in young infected mice on OA-ED as compared to old infected OA-ED mice (p=0.036).

Conclusion
Advanced age is associated with higher expression levels of the insulin-independent glucose transporter GLUT1, independent of the infection status. This implicates a switch towards a preferred cardiac glucose utilization for ATP generation in older and diseased mice. OA-ED resulted in an induction of fatty acid metabolism markers in young mice. The findings suggest higher metabolic flexibility in young mice and a distinct protective effect of OA-ED in the setting of gingival infection. While the underlying pathways need further investigation, infection and advanced age seem to trigger a metabolic phenotype of less efficient glucose utilization in the heart that is partially reversible under OA-ED in young mice.Thereby, our animal model data point towards preventive nutritional substitution strategies that might offer health benefits to address increased cardiac and periodontal disease susceptibility and associated economic burden.

Figure: Western Blot analysis of GLUT1. ND = normal diet, OA = oleic acid-enriched diet, PA = palmitic acid-enriched diet, (+) P. gingivalis infection, (-) PBS infection (placebo)