CALL FOR PAPERS Fetal and Neonatal Programming: Epigenetic Modification of Phenotype High-fat/fructose feeding during prenatal and postnatal development in female rats increases susceptibility to renal and metabolic injury later in life

Flynn ER, Alexander BT, Lee J, Hutchens Jr ZM, MaricBilkan C. High-fat/fructose feeding during prenatal and postnatal development in female rats increases susceptibility to renal and metabolic injury later in life. Am J Physiol Regul Integr Comp Physiol 304: R278–R285, 2013. First published December 19, 2012; doi:10.1152/ajpregu.00433.2012.—Accumulating evidence suggests that both an adverse prenatal and early postnatal environment increase susceptibility to renal and metabolic dysfunction later in life; however, whether exposure to adverse conditions during both prenatal and postnatal development act synergistically to potentiate the severity of renal and metabolic injury remains unknown. Sprague-Dawley rats were fed either a standard diet or a diet high in fat/fructose throughout pregnancy and lactation. After being weaned, female offspring were randomized to either standard diet or the high-fat/high-fructose diet, resulting in the following treatment groups: NF-NF, offspring of mothers fed a standard diet and fed a standard diet postnatally; NF-HF, offspring of mothers fed a standard diet and fed a high-fat/ fructose diet postnatally; HF-NF, offspring of mothers fed a high-fat/ fructose diet and fed a standard diet postnatally; HF-HF, offspring of mothers fed a high-fat/fructose diet and fed a high-fat/fructose diet postnatally. At the time of euthanasia (17 wk of age), HF-HF offspring weighed 30% more and had 110% more visceral fat than NF-NF offspring. The HF-HF offspring also had elevated blood glucose levels, glucose intolerance, 286% increase in urine albumin excretion, and 60% increase in glomerulosclerosis compared with NF-NF. In addition, HF-HF offspring exhibited a 100% increase in transforming growth factorprotein expression and 116% increase in the abundance of infiltrated macrophages compared with the NF-NF offspring. These observations suggest that high-fat/fructose feeding during prenatal and throughout postnatal life increases the susceptibility to renal and metabolic injury later in life.