The effect of pivalate treatment of pregnant rats on body mass and insulin levels in the adult offspring

Pivalic acid is used as a prodrug to increase gut absorption of a variety of different antibiotics. Pivalic acid is also known to induce a number of metabolic aberrations which may be in part explained by concurrent mild carnitine depletion. Rat pups (5 days old) born to mothers treated throughout their pregnancy and lactation period with sodium pivalate, showed an increase in liver and muscle triglycerides and elevated plasma ketone bodies, compared to controls. A reduction of free carnitine content in liver, muscle and plasma was also observed in the pivalate treated group. In a second study, pups were treated with either pivalate for 24 days (females), or pivalate for 120 days (males). Both groups were fed standard diets. In both groups (male and female), the pivalate treatment showed a statistically significant hyperinsulinaemia and an increase of body mass compared with that of age- and sex-matched control groups. In addition, after a glucose loading, significantly higher levels of insulin in the pivalate-treated group (male) with respect to controls were observed. In conclusion, our data suggest that maternal pivalate treatment may predispose adult offspring to developing insulin-resistance and obesity.