Soon Ok Kim1, Graham Aberdeen2, Terrie J Lynch1, Eugene D Albrecht2, Gerald J Pepe1. 1. Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA. 2. Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Abstract
PURPOSE: We recently demonstrated that offspring delivered to baboons deprived of estrogen during the second half of gestation exhibited insulin resistance. Therefore, because skeletal muscle accounts for >80% of insulin dependent glucose disposal, we suggested that estrogen in utero programs factors in fetal skeletal muscle important for insulin sensitivity in offspring. However, liver and adipose are also sites of insulin action and adipose insulin resistance can increase serum free fatty acid (FFA) levels and thereby reduce skeletal muscle insulin sensitivity. Therefore, in the current study we determined whether estrogen-deprived offspring exhibit normal adipose and hepatic function. RESULTS: The fasting serum levels of adiponectin, leptin, glucose, and analytes of liver function as well as the basal levels of serum FFA were similar in offspring of estrogen replete/suppressed baboons. Moreover, the normal glucose-induced decline in serum FFA levels measured in untreated offspring was also measured in offspring of letrozole-treated baboons. Fetal serum levels of adiponectin and leptin in late gestation also were similar and expression of nitrotyrosine negligible in fetal liver and adipose of untreated and letrozole-treated animals. CONCLUSIONS: These results indicate that offspring of letrozole-treated baboons have normal adipose and liver function and do not exhibit adipose insulin resistance. Therefore, we suggest that the insulin resistance observed in estrogen-deprived offspring primarily reflects a decline in insulin-stimulated glucose clearance by skeletal muscle and which supports our original suggestion that estrogen in utero programs factors in fetal skeletal muscle that promote insulin sensitivity in offspring.
PURPOSE: We recently demonstrated that offspring delivered to baboons deprived of estrogen during the second half of gestation exhibited insulin resistance. Therefore, because skeletal muscle accounts for >80% of insulin dependent glucose disposal, we suggested that estrogen in utero programs factors in fetal skeletal muscle important for insulin sensitivity in offspring. However, liver and adipose are also sites of insulin action and adipose insulin resistance can increase serum free fatty acid (FFA) levels and thereby reduce skeletal muscle insulin sensitivity. Therefore, in the current study we determined whether estrogen-deprived offspring exhibit normal adipose and hepatic function. RESULTS: The fasting serum levels of adiponectin, leptin, glucose, and analytes of liver function as well as the basal levels of serum FFA were similar in offspring of estrogen replete/suppressed baboons. Moreover, the normal glucose-induced decline in serum FFA levels measured in untreated offspring was also measured in offspring of letrozole-treated baboons. Fetal serum levels of adiponectin and leptin in late gestation also were similar and expression of nitrotyrosine negligible in fetal liver and adipose of untreated and letrozole-treated animals. CONCLUSIONS: These results indicate that offspring of letrozole-treated baboons have normal adipose and liver function and do not exhibit adipose insulin resistance. Therefore, we suggest that the insulin resistance observed in estrogen-deprived offspring primarily reflects a decline in insulin-stimulated glucose clearance by skeletal muscle and which supports our original suggestion that estrogen in utero programs factors in fetal skeletal muscle that promote insulin sensitivity in offspring.
Authors: David H Abbott; Cristin R Bruns; Deborah K Barnett; Andrea Dunaif; Theodore L Goodfriend; Daniel A Dumesic; Alice F Tarantal Journal: Am J Physiol Endocrinol Metab Date: 2010-08-03 Impact factor: 4.310
Authors: Graham W Aberdeen; Ahmet A Baschat; Chris R Harman; Carl P Weiner; Patricia W Langenberg; Gerald J Pepe; Eugene D Albrecht Journal: Am J Physiol Heart Circ Physiol Date: 2009-12-18 Impact factor: 4.733
Authors: Eugene D Albrecht; Graham W Aberdeen; Jeffery S Babischkin; Steven J Prior; Terrie J Lynch; Irene A Baranyk; Gerald J Pepe Journal: Endocrinology Date: 2022-05-01 Impact factor: 5.051