Objective Pioglitazone (PIO), an antidiabetic drug of the thiazolidinedione family, improves glucose and lipid metabolism in muscle, adipose, and liver tissues via peroxisome proliferator-activated receptor gamma (PPARγ) activation. We hypothesize that PIO therapy will improve the metabolic status of offspring exposed to maternal obesity in a mouse model developmentally programmed for metabolic syndrome (MetS). Study Design CD-1 female mice were fed a high-fat diet for 3 months prior to breeding and throughout pregnancy and lactation. The pups were weaned to a standard-fat diet. Offspring were randomly assigned to receive 40 mg/kg of PIO in 0.5% of methyl cellulose or 0.5% methyl cellulose by daily oral gavage for 2 weeks. The pre- and post-treatment total body weights of the pups were recorded. Visceral (VAT) and subcutaneous (SAT) adipose tissue were evaluated using micro-computed tomography. Serum analytes were measured. Post-treatment, minimally invasive microendoscopic fluorescence confocal imaging and intraperitoneal glucose tolerance tests were performed. The data were analyzed using appropriate statistical tests (significance, P<0.05). Results PIO therapy resulted in lower total body weight and lower VAT gain, and increased SAT. PIO significantly lowered triglyceride, insulin levels, and HOMA-IR in males, and fasting glucose in females. There was a trend toward larger adipocyte size. Conclusion Short-term PIO therapy in the offspring of obese mothers attenuates metabolic changes associated with the developmental programming of metabolic syndrome. These novel data suggest a potential role for drugs that activate PPARγ receptors to prevent MetS in the adult offspring at risk to develop metabolic alterations.

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