Neonatal Vitamin C and Cysteine Deficiencies Program Adult Hepatic Glutathione and Specific Activities of Glucokinase, Phosphofructokinase, and Acetyl-CoA Carboxylase in Guinea Pigs’ Livers

Abstract

Premature neonates are submitted to an early-life oxidative stress from parenteral nutrition, which is vitamin C (VC) deficient and induces low endogenous levels of glutathione. The oxidative stress caused by these deficiencies may permanently affect liver glycolysis and lipogenesis. This study evaluates the short- and long-term effects of neonatal VC and cysteine deficient diets on redox and energy metabolism. Three-day-old Hartley guinea pigs from both sexes were given a regular or a deficient diet (VC, cysteine, or both) until week 1 of life. Half of the animals were sacrificed at this age, while the other half ate a complete diet until 12 weeks. Liver glutathione and the activity and protein levels of glucokinase, phosphofructokinase, and acetyl-CoA-carboxylase were measured. Statistics: factorial ANOVA (5% threshold). At 1 week, all deficient diets decreased glutathione and the protein levels of glucokinase and phosphofructokinase, while cysteine deficiency decreased acetyl-CoA-carboxylase levels. A similar enzyme level was observed in control animals at 12 weeks. At this age, VC deficiency decreased glutathione, while cysteine increased it. Acetyl-CoA-carboxylase protein levels were increased, which decreased its specific activity. Early-life VC and cysteine deficiencies induce neonatal oxidative stress and an adult-like metabolism, while predisposing to increased lipogenic rates during adulthood.

Disturbances of the Lung Glutathione System in Adult Guinea Pigs Following Neonatal Vitamin C or Cysteine Deficiency

“…During sacrifice, lungs and liver were collected and quickly frozen at −80 • C and kept at this temperature until biochemical determinations. The study experimental design, including diet composition, has been published before [7].…”

“…Ascorbate was resolved in a 50 µM/45 cm silica capillary, 25 • C, 30 kV in an Agilent 7100 Capillary Electrophoresis System (Agilent Technologies, Mississauga, ON, Canada). Separation was performed in boric acid 200 mM and acetonitrile 20% v/v buffer, pH 9.6, and detection of ascorbate was performed by absorbance at 268 nm [7,21].…”

“…We have demonstrated that vitamin C and cysteine deficiencies lead to higher cytoplasmic Nrf2 in the neonatal liver of guinea pigs with decreased translocation of Nrf2 into the nucleus at adult life [7]. Nrf2 is the master regulator of the antioxidant response.…”

“…Very premature birth (≤32 weeks of gestation) is associated with several short-and long-term consequences over the development of several diseases. In neonatal life, infants born prematurely develop complications such as bronchopulmonary dysplasia [1], and they are at higher risk of developing asthma, chronic obstructive pulmonary disease (COPD) and other respiratory complications in adulthood [2,3], as well as other complications [1,2,[4][5][6][7][8][9][10][11]. Despite the strong clinical evidence, it is challenging to seize what specific aspects of prematurity lead to the increased risk of neonatal and adult diseases.…”

Effects of RNA Interference with Acetyl-CoA Carboxylase Gene on Expression of Fatty Acid Metabolism-Related Genes in Macrobrachium rosenbergii under Cold Stress

“…Previous studies on the ACC gene in medicine have found that cancer cells can reprogram the lipid metabolism during malignant progression, and ACC plays a key role in regulating the growth and differentiation of leukemic initiation cells. In addition, adenosine monophosphate-activated protein kinase (AMPK) can inhibit ACC, reduce the consumption of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) in fatty acid synthesis, and generate homeostasis [22][23][24]. At present, there are few studies on the changes in ACC gene expression in aquatic animals under cold stress.…”