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Pioglitazone therapy in mouse offspring exposed to maternal obesity
Arshag Kalanderian1, Nicola Abate, Igor Patrikeev
1Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA.
Insights
Pioglitazone (PIO) therapy in offspring of obese mothers improved metabolic health, reducing body weight and visceral fat while enhancing insulin sensitivity. This suggests a potential preventative role for PPAR-gamma activators against metabolic syndrome.
Area of Science:
- Endocrinology and Metabolism
- Developmental Programming
- Pharmacology
Background:
- Maternal obesity can lead to developmental programming of metabolic syndrome in offspring.
- Thiazolidinediones, like pioglitazone (PIO), activate peroxisome proliferator-activated receptor gamma (PPARγ) to improve glucose and lipid metabolism.
Purpose of the Study:
- To investigate the efficacy of PIO therapy in mitigating metabolic dysfunction in offspring exposed to maternal obesity.
- To determine if PIO can prevent the developmental programming of metabolic syndrome.
Main Methods:
- CD-1 mice dams were fed a high-fat diet during gestation and lactation.
- Offspring were treated with PIO (40 mg/kg) or methylcellulose for two weeks.
- Body weight, adipose tissue (visceral and subcutaneous), serum analytes, and glucose tolerance were assessed.
Main Results:
- PIO treatment reduced offspring body weight and visceral adipose tissue gain, while increasing subcutaneous adipose tissue.
- Significant improvements were observed in triglyceride levels, insulin levels, and insulin resistance (HOMA-IR) in males, and fasting glucose in females.
- A trend towards increased adipocyte size was noted.
Conclusions:
- Short-term pioglitazone therapy effectively attenuates metabolic alterations in offspring of obese mothers.
- These findings highlight a potential therapeutic strategy using PPARγ activators to prevent metabolic syndrome in at-risk individuals.
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.
