期刊
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
卷 208, 期 4, 页码 -出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.ajog.2013.01.013
关键词
fetal programming; in vivo adipose tissue imaging; maternal obesity; mice; offspring; pioglitazone
资金
- NCATS NIH HHS [UL1TR000071, UL1 TR000071] Funding Source: Medline
- NICHD NIH HHS [K12HD052023, K12 HD052023] Funding Source: Medline
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 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. 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 and subcutaneous adipose tissue were evaluated using microcomputed tomography. Serum analytes were measured. After treatment, minimally invasive microendoscopic fluorescence confocal imaging and intraperitoneal glucose tolerance tests were performed. The data were analyzed using appropriate statistical tests (significance, P < .05). RESULTS: PIO therapy resulted in lower total body weight and lower visceral adipose tissue gain and increased subcutaneous adipose tissue. PIO significantly lowered triglycerides, insulin levels, and homeostasis model assessment of insulin resistance 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 peroxisome proliferator-activated receptor gamma receptors to prevent metabolic syndrome in the adult offspring at risk to develop metabolic alterations.
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