title: Pioglitazone therapy in mouse offspring exposed to maternal obesity.
abstract: 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.
  
  
  METHODS
  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 posttreatment 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA.
authors: Arshag
authors: A
authors: Kalanderian
authors: Nicola
authors: N
authors: Abate
authors: Igor
authors: I
authors: Patrikeev
authors: Jingna
authors: J
authors: Wei
authors: Kathleen Listiak
authors: KL
authors: Vincent
authors: Massoud
authors: M
authors: Motamedi
authors: George Robert
authors: GR
authors: Saade
authors: Egle
authors: E
authors: Bytautiene
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D009765:Obesity / Q000150:complications*; D047495:PPAR gamma; D000077205:Pioglitazone; D011247:Pregnancy; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone