PT  - JOURNAL ARTICLE
AU  - Letizia Guiducci
AU  - Silvia Burchielli
AU  - Vlad Chubuchny
AU  - Rosa Sicari
AU  - Tiziana Liistro
AU  - Anca I. Corciu
AU  - Silvia Pardini
AU  - Pietro Di Cecco
AU  - Samantha Manfredi
AU  - Marco Bucci
AU  - Piero A. Salvadori
AU  - Maria Grazia Andreassi
AU  - Patricia Iozzo
TI  - Maternal and Sex Dependency of Insulin Resistance: Longitudinal PET and Echocardiography Study from the Healthy Fetus to the Adult Minipig
AID  - 10.2967/jnumed.111.087882
DP  - 2011 Dec 01
TA  - Journal of Nuclear Medicine
PG  - 1993--2000
VI  - 52
IP  - 12
4099  - http://jnm.snmjournals.org/content/52/12/1993.short
4100  - http://jnm.snmjournals.org/content/52/12/1993.full
SO  - J Nucl Med2011 Dec 01; 52
AB  - 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.