A Short-Term Fasting in Neonates Induces Breathing Instability and Epigenetic Modification in the Carotid Body

Abstract

The respiratory control system is not fully developed in newborn, and data suggest that adequate nutrition is important for the development of the respiratory control system. Infants need to be fed every 2–4 h to maintain appropriate energy levels, but a skip of feeding can occur due to social economical reasons or mild sickness of infants. Here, we asked questions if a short-term fasting (1) alters carotid body (CB) chemoreceptor activity and integrated function of the respiratory control system; (2) causes epigenetic modification within the respiratory control system. Mouse pups (<P14) were fasted for 3–6 h. Breathing became irregular and slow. The number and duration of apnea increased. Ventilatory response to hypoxia was also depressed even after the pups were returned to own dams. These effects were more prominent when the pups were younger and fasting time was longer. The hypoxic response of the carotid sinus nerve activity appeared to be depressed after fasting. Moreover, fasting increased global 5mC and 5-hmC content in DNA isolated from the CB but not DNA in the superior cervical ganglion (SCG). Methylation specific PCR (MSPCR) revealed that fasting increased methylation of leptin and socs3 genes. The results suggest fasting inhibits CB activity leading to hypoventilation, and low glucose does not compensate the low CB activity. Epigenetic effect on CB function/activity may be related to the prolonged effect of fasting on ventilation.

Multigenerational inheritance of breathing deficits following perinatal exposure to titanium dioxide nanoparticles in the offspring of mice

“…Thus, our results suggest a delayed maturation of the respiratory function in exposed pups that could be related to a metabolic distress [ 6 ]. Notably, the maternal and pup's diet directly influences offspring body weight and breathing [ 31 – 33 ]. Interestingly, newborn mice subjected to fasting (3–6 h) exhibited breathing instability characterized by decreased breathing frequency and increased occurrence of apneas [ 33 ].…”

“…Notably, the maternal and pup's diet directly influences offspring body weight and breathing [ 31 – 33 ]. Interestingly, newborn mice subjected to fasting (3–6 h) exhibited breathing instability characterized by decreased breathing frequency and increased occurrence of apneas [ 33 ]. Despite these important findings, the mechanisms linking impaired neonatal growth and breathing alterations remain unclear.…”

Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities

“…Moreover, ketone bodies (β-hydroxybutyrate and acetoacetate) have an impact on epigenetic factors. They restrain the histone deacetylase 1 (HDAC1) activity, and promote PTMs of proteins by butyrylation, affecting DNA methylation and acetylating histone and non-histone proteins [187,[192][193][194][195].…”

Ketogenic Diets in Pancreatic Cancer and Associated Cachexia: Cellular Mechanisms and Clinical Perspectives

“…At the molecular level, βHB and ACA affect epigenetic marks by inhibiting HDAC1, and this modulates protein expression at the post-translational level, affecting DNA methylation and acetylating histone and non-histone proteins [ 125 , 126 , 127 ]. Of note, evidence also suggests that βHB can have a direct epigenetic effect via a novel histone modification known as β-hydroxybutyrlation of H3K9, which results in improved gene regulation [ 128 ].…”