Pioglitazone therapy in mouse offspring exposed to maternal obesity

Arshag Kalanderian, Nicola Abate, Igor Patrikeev, Jingna Wei, Kathleen Vincent, Massoud Motamedi, George Saade, Egle Bytautiene

Research output: Contribution to journalArticle

9 Citations (Scopus)

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. 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 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. 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.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume208
Issue number4
DOIs
StatePublished - Apr 2013

Fingerprint

pioglitazone
Obesity
Mothers
Methylcellulose
Intra-Abdominal Fat
PPAR gamma
Subcutaneous Fat
Therapeutics
Body Weight
Glucose
X-Ray Microtomography
Optical Imaging
High Fat Diet
Glucose Tolerance Test
Lipid Metabolism
Lactation
Hypoglycemic Agents
Adipocytes
Breeding
Insulin Resistance

Keywords

  • fetal programming
  • in vivo adipose tissue imaging
  • maternal obesity
  • mice
  • offspring
  • pioglitazone

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Pioglitazone therapy in mouse offspring exposed to maternal obesity. / Kalanderian, Arshag; Abate, Nicola; Patrikeev, Igor; Wei, Jingna; Vincent, Kathleen; Motamedi, Massoud; Saade, George; Bytautiene, Egle.

In: American Journal of Obstetrics and Gynecology, Vol. 208, No. 4, 04.2013.

Research output: Contribution to journalArticle

Kalanderian, Arshag ; Abate, Nicola ; Patrikeev, Igor ; Wei, Jingna ; Vincent, Kathleen ; Motamedi, Massoud ; Saade, George ; Bytautiene, Egle. / Pioglitazone therapy in mouse offspring exposed to maternal obesity. In: American Journal of Obstetrics and Gynecology. 2013 ; Vol. 208, No. 4.
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