Prenatal and early postnatal exposure to high-saturated-fat diet represses Wnt signaling and myogenic genes in offspring rats

Abstract

The prenatal and early postnatal period is a key developmental window for nutrition status, and high-fat exposure in this period has been shown to be associated with type 2 diabetes, obesity and other features of metabolic disorders later in life. The present study was designed to investigate the underlying molecular mechanisms and role of relative genes involved in this process. We investigated the impact of prenatal and early postnatal exposure to a high-saturated-fat diet on the regulation of the Wnt signaling pathway and myogenic genes in skeletal muscle of rat offspring as well as the serum and muscle physiological outcomes. Timed-pregnant Sprague-Dawley rats were fed either a control (C, 16% kcal fat) or high-saturated-fat diet (HF, 45% kcal fat) throughout gestation and lactation. After weaning, female offspring were fed a control diet to generate two offspring groups: control diet-fed offspring of control diet-fed dams (C/C) and control diet-fed offspring of HF diet-fed dams (HF/C). The serum glucose of the HF/C offspring (5.58 ± 0.26 mmol/L) was significantly higher than that of C/C offspring (4.97 ± 0.28 mmol/L), and the Homeostasis Model Assessment-Insulin Resistance of HF/C offspring (2.00 ± 0.11) was also significantly higher when compared with C/C (1.84 ± 0.09). Furthermore, HF/C offspring presented excessive intramuscular fat accumulation (1.8-fold, P < 0.05) and decreased muscle glycogen (1.3-fold, P < 0.05), as well as impairment of muscle development at the age of 12 weeks. Meanwhile, we observed the repression of Wnt/ β-catenin signaling and myogenic genes in HF/C offspring. The present study indicates that prenatal and early postnatal exposure to a high-saturated-fat diet suppresses the development of skeletal muscle and myogenic genes via Wnt/ β-catenin signaling, and the inappropriate muscle development could potentially contribute to the predisposition of offspring to develop metabolic-syndrome-like phenotype in adulthood.