Obesity has reached epidemic proportions worldwide. Several animal models of
obesity exist, but studies are lacking that compare traditional
lard-based high fat diets (HFD) to "Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid
weight gain, markers of
Metabolic Syndrome, multi-tissue
lipid accumulation, and dramatic
inflammation. To identify potential mediators of CAF-induced
obesity and
Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of
fatty acids and acylcarnitines. These increases in metabolites were associated with systemic
mitochondrial dysfunction that paralleled
weight gain, physiologic measures of
Metabolic Syndrome, and tissue
inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of
inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory
saturated fatty acids and oxidation intermediates laurate and lauroyl
carnitine. Treatment of bone marrow-derived macrophages with lauroyl
carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory
cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human
obesity, which models
Metabolic Syndrome-related
mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of
saturated fatty acids may limit the
inflammation associated with
obesity leading to
Metabolic Syndrome.