Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation
Figure 6
Cafeteria diet drives accumulation of oxidative intermediates and pro-inflammatory lipid mediators.
Rats were fed SC or CAF diets for 10 weeks and at sacrifice serum and was isolated for metabolomic analysis including total and individual non-esterified fatty acids (NEFA), acylcarnitine and amino acid metabolite profiling of serum and muscle. To compare the effects of traditional defined lard-based diets with a CAF model on adipose metabolism, rats were fed SC, low fat and high fat lard-based defined diets, or CAF diet for 15 weeks and metabolites were analyzed. A. Metabolomic profiling has revealed that CAF diet-induced obesity drives accumulation of non-esterified fatty acids (NEFA), triglycerides (TG), and fatty acid β-oxidation intermediates in serum, muscle and for the first time white adipose tissue. CAF-mediated effects in adipose are more exaggerated than lard-based HFD effects. B. Lauroyl carnitine, an adipose-derived biomarker identified through metabolomic profiling was demonstrated to drive polarization of primary bone marrow derived macrophages (BMDM) towards the pro-inflammatory “M1" phenotype. Taken together, CAF diet proved to be a rapid and dramatic inducer of insulin resistance, components of Metabolic Syndrome, and metabolic biomarkers. In CAF-diet-induced obese adipose, lauroyl carnitine was identified as a potential mediator between metabolism of saturated fatty acids and the pro-inflammatory response.