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

Pivalic acid is used as a prodrug to increase gut absorption of a variety o f different antibiotics. Pivalic acid is also known to induce a number of m etabolic aberrations which may be in part explained by concurrent mild carn itine depletion. Rat pups (5 days old) born to mothers treated throughout t heir pregnancy and lactation period with sodium pivalate, showed an increas e in liver and muscle triglycerides and elevated plasma ketone bodies, comp ared to controls. A reduction of free carnitine content in liver, muscle an d 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 significan t hyperinsulinaemia and an increase of body mass compared with that of age- and sex-matched control groups. In addition, after a glucose loading, sign ificantly higher levels of insulin in the pivalate-treated group (male) wit h respect to controls were observed. In conclusion, our data suggest that m aternal pivalate treatment may predispose adult offspring to developing ins ulin-resistance and obesity. (C) 2001 Elsevier Science Inc. All rights rese rved.