Obesity leads to the development of
nonalcoholic fatty liver disease (
NAFLD) and associated alterations to the plasma
proteome. To elucidate the underlying changes associated with
obesity, we performed liquid chromatography-tandem mass spectrometry in the liver and plasma of obese
leptin-deficient ob/ob mice and integrated these data with publicly available transcriptomic and proteomic datasets of
obesity and
metabolic diseases in preclinical and clinical cohorts. We quantified 7173 and 555
proteins in the liver and plasma
proteomes, respectively. The abundance of
proteins related to
fatty acid metabolism were increased, alongside peroxisomal proliferation in ob/ob liver. Putatively secreted
proteins and the secretory machinery were also dysregulated in the liver, which was mirrored by a substantial alteration of the plasma
proteome. Greater than 50% of the
plasma proteins were differentially regulated, including
NAFLD biomarkers,
lipoproteins, the
20S proteasome, and the
complement and coagulation cascades of the immune system. Integration of the liver and plasma
proteomes identified
proteins that were concomitantly regulated in the liver and plasma in
obesity, suggesting that the systemic abundance of these
plasma proteins is regulated by secretion from the liver. Many of these
proteins are systemically regulated during
type 2 diabetes and/or
NAFLD in humans, indicating the clinical importance of liver-plasma cross talk and the relevance of our investigations in ob/ob mice. Together, these analyses yield a comprehensive insight into
obesity and provide an extensive resource for
obesity research in a prevailing model organism.