Maternal and Sex Dependency of Insulin Resistance: Longitudinal PET and Echocardiography Study from the Healthy Fetus to the Adult Minipig

Journal of Nuclear Medicine

Samantha Manfredi¹  Anca I. Corciu¹  Pietro Di Cecco¹  Patricia Iozzo¹  Rosa Sicari¹  Tiziana Liistro¹  Maria Grazia Andreassi¹  Marco Bucci¹  Piero A. Salvadori¹  Silvia Pardini¹  Silvia Burchielli¹  Letizia Guiducci¹  Vlad Chubuchny¹ 

关键词: PET;    DNA damage;    fetal imaging;    myocardial glucose uptake;   

DOI  :  10.2967/jnumed.111.087882

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Cardiovascular and metabolic vulnerability have an early developmental origin. We evaluated the potential influence of innate life factors, including the metabolism of the mother and the sex of the offspring, on cardiometabolic risk, including organ-specific insulin resistance, subclinical cardiac dysfunction, and DNA oxidative damage throughout the lifespan. Methods: Two female minipigs were studied during late pregnancy, and their offspring were restudied at the ages of 1 mo (n = 11), 6 mo (n = 9), and 9 mo (n = 10, 6 offspring and 4 age-matched animals). We measured insulin-mediated glucose disposal in skeletal muscle, adipose tissue, liver, and myocardium using 18F-FDG PET; cardiac function using 2-dimensional strain echocardiography; and DNA damage using the comet assay. Results: Glucose metabolism showed the 2 sows to have differences similar to those in their respective 1-mo-old offspring. Over time, compared with female animals, male animals developed myocardial insulin resistance (male animals vs. female animals: 34 ± 5 vs. 58 ± 8 μmol/min/kg at 6 mo, P = 0.03; 29 ± 8 vs. 60 ± 7 μmol/min/kg at 9 mo, P = 0.02). Cardiac function progressively deteriorated in male animals from 1 mo (radial strain, −60% ± 7%; strain rate, −5.4 ± 0.9 s−1) to 6 mo (radial strain, −41% ± 5%; strain rate, −2.5 ± 0.2 s−1, P < 0.05 vs. 1 mo) and 9 mo (radial strain, −32% ± 5%; strain rate, −1.6 ± 0.2 s−1, P < 0.01 vs. 1 mo) and was significantly different from that in female animals (radial strain, −48% ± 4%; strain rate, −3.1 ± 0.2 s−1, P < 0.05 and P < 0.01, respectively). Oxidative damage was reduced in female animals and increased in male animals across age categories (P < 0.05). Conclusion: The metabolism of minipig offspring is influenced by maternal insulin sensitivity during early life stages. Sex-related effects prevail thereafter in healthy minipigs, documenting a precocious onset of cardiometabolic vulnerability in male offspring.

【 授权许可】

Unknown