Pyrroloquinoline quinone attenuated benzyl butyl phthalate induced metabolic aberration and a hepatic metabolomic analysis

Benzyl butyl phthalate (BBP) has recently been implicated as an obesogen. Our recent study demonstrated that BBP can exacerbate high fat diet (HFD) induced diabesity in male mice. Here, we explored if pyrroloquinoline quinone (PQQ), a natural antioxidant and phytochemical, can attenuate metabolic aberrations induced by HFD or HFD-BBP combination. C57Bl/6 male and female mice were fed either a chow diet (CD) or HFD with or without BBP (3 mg/kg body weight/day) and/or PQQ (20 mg/kg/day) for 16 weeks. The mice's body and tissue weight, fasting blood glucose, glucose and insulin tolerance test, and liver metabolites level were measured. In HFD-fed male mice, PQQ significantly attenuated the increased body weight, liver weight, fasting blood glucose, and insulin intolerance under BBP exposure. Even though female mice did show some reversal of metabolic characteristics by PQQ, the response was not similar nor consistent with the male population. Among the 14 hepatic metabolites that were significantly altered by HFD compared to CD, only three major metabolites (acetylL-carnitine, DL-stachytine, and propionylcarnitine) were decreased. These three were shown to have more reduction under BBP exposure in the presence of HFD whereas with addition of PQQ, these metabolites were restored. Pathway analysis and literature search revealed that these metabolites were negatively associated with obesity and were involved in several pathways including beta-oxidation, oxidative stress, and mitochondrial function. Overall, this finding indicated the potential use of PQQ to restore the wide range of aberrant metabolic effect induced by an obesogen in the presence of a western diet.