The Plasma Free Fatty Acid Carrier Proteome is Altered in Diet‐Induced and Genetically Obese Mice

OBJECTIVE: We aimed to examine the effect of obesity on the plasma free fatty acid (FFA) carrier proteome in mice. METHODS: From 6 to 20 weeks of age, male and female C57BL/6J wild-type mice were fed either a low-fat diet (10% of kilocalories from fat) or a high-fat diet (60% of kilocalories from fat), and leptin-deficient ob/ob mice were fed a low-fat diet. Plasma FFA carrier proteins were isolated using a fatty acid pulldown assay and detected by proteomics. Plasma proteins and lipoprotein particles were separated by fast protein liquid chromatography (FPLC). Hepatic gene expression was quantified by qPCR. RESULTS: In each sex, 284 FFA carrier proteins were detected, with dozens of differentially abundant proteins between lean and obese groups. We identified eight proteins that exhibited altered abundance in both models of obesity for both sexes, with the majority transcribed in the liver. Interestingly, proteins with lower or higher abundance in the plasma FFA carrier proteome in obesity showed correspondingly altered gene expression in the liver. Furthermore, FFAs coeluted with lipoprotein particles in FPLC fractions, with accentuated FFA levels in the low-density lipoprotein fractions in obesity. CONCLUSIONS: Obesity remodels the spectrum of plasma FFA carriers, potentially via changes in gene expression and lipoprotein abundance.