Metabolic Activity of Human Embryos after Thawing Differs in Atmosphere with Different Oxygen Concentrations

The vitrification of human embryos is more and more frequently being utilized as a method of assisted reproduction. For this technique, gentle treatment of the embryos after thawing is crucial. In this study, the balance of amino acids released to/consumed from the cultivation media surrounding the warmed embryos was observed in the context of a cultivation environment, which was with the atmospheric oxygen concentration ≈20% or with a regulated oxygen level—hysiological (5%). It is the first time that total amino acid turnover in human embryos after their freezing at post compaction stages has been evaluated. During this study, progressive embryos (developed to blastocyst stage) and stagnant embryos (without developmental progression) were analyzed. It was observed that the embryos cultivated in conditions of physiological oxygen levels (5% oxygen) showed a significantly lower consumption of amino acids from the cultivation media. Progressively developing embryos also had significantly lower total amino acid turnovers (consumption and production of amino acids) when cultured in conditions with physiological oxygen levels. Based on these results it seems that a cultivation environment with a reduced oxygen concentration decreases the risk of degenerative changes in the embryos after thawing. Therefore, the cultivation of thawed embryos in an environment with physiological oxygen levels may preclude embryonal stagnation, and can support the further development of human embryos after their thawing.

Nonessential amino acid usage for protein replenishment in humans: a method of estimation

ABSTRACT Background Essential amino acids (EAAs) are key factors in determining dietary protein quality. Their RDAs have been estimated. However, although nonessential amino acids (NEAAs) are utilized for protein synthesis too, no estimates of their usage for body protein replenishment have been proposed so far. Objective The aim of this study was to provide minimum, approximate estimates of NEAA usage for body protein replenishment/conservation in humans. Methods A correlation between the pattern of both EAAs and NEAAs in body proteins, and their usage, was assumed. In order to reconstruct an “average” amino acid pattern/composition of total body proteins (as grams of amino acid per gram of protein), published data of relevant human organs/tissues (skeletal muscle, liver, kidney, gut, and collagen, making up ∼74% of total proteins) were retrieved. The (unknown) amino acid composition of residual proteins (∼26% of total proteins) was assumed to be the same as for the sum of the aforementioned organs excluding collagen. Using international EAA RDA values, an average ratio of EAA RDA to the calculated whole-body EAA composition was derived. This ratio was then used to back-calculate NEAA usage for protein replenishment. The data were calculated also using estimated organ/tissue amino acid turnover. Results The individual ratios of World Health Organization/Food and Agriculture Organization/United Nations University RDA to EAA content ranged between 1.35 (phenylalanine + tyrosine) and 3.68 (leucine), with a mean ± SD value of 2.72 ± 0.81. In a reference 70-kg subject, calculated NEAA usage for body protein replenishment ranged from 0.73 g/d for asparagine to 3.61 g/d for proline. Use of amino acid turnover data yielded similar results. Total NEAA usage for body protein replenishment was ∼19 g/d (45% of total NEAA intake), whereas ∼24 g/d was used for other routes. Conclusion This method may provide indirect minimum estimates of the usage of NEAAs for body protein replacement in humans.

The Liver–α-Cell Axis and Type 2 Diabetes

Both type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD) strongly associate with increasing body mass index, and together these metabolic diseases affect millions of individuals. In patients with T2D, increased secretion of glucagon (hyperglucagonemia) contributes to diabetic hyperglycemia as proven by the significant lowering of fasting plasma glucose levels following glucagon receptor antagonist administration. Emerging data now indicate that the elevated plasma concentrations of glucagon may also be associated with hepatic steatosis and not necessarily with the presence or absence of T2D. Thus, fatty liver disease, most often secondary to overeating, may result in impaired amino acid turnover, leading to increased plasma concentrations of certain glucagonotropic amino acids (e.g., alanine). This, in turn, causes increased glucagon secretion that may help to restore amino acid turnover and ureagenesis, but it may eventually also lead to increased hepatic glucose production, a hallmark of T2D. Early experimental findings support the hypothesis that hepatic steatosis impairs glucagon’s actions on amino acid turnover and ureagenesis. Hepatic steatosis also impairs hepatic insulin sensitivity and clearance that, together with hyperglycemia and hyperaminoacidemia, lead to peripheral hyperinsulinemia; systemic hyperinsulinemia may itself contribute to worsen peripheral insulin resistance. Additionally, obesity is accompanied by an impaired incretin effect, causing meal-related glucose intolerance. Lipid-induced impairment of hepatic sensitivity, not only to insulin but potentially also to glucagon, resulting in both hyperinsulinemia and hyperglucagonemia, may therefore contribute to the development of T2D at least in a subset of individuals with NAFLD.

Divergent metabolic substrate utilization in brain during epileptogenesis precedes chronic hypometabolism

Alterations in metabolism during epileptogenesis may be a therapy target. Recently, an increase in amino acid transport into the brain was proposed to play a role in epileptogenesis. We aimed to characterize alterations of substrate utilization during epileptogenesis and in chronic epilepsy. The lithium-pilocarpine post status epilepticus (SE) rat model was used. We performed longitudinal O-(2-[(18)F]fluoroethyl)-l-tyrosine (18F-FET) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and calculated 18F-FET volume of distribution (Vt) and 18F-FDG uptake. Correlation analyses were performed with translocator protein-PET defined neuroinflammation from previously acquired data. We found reduced 18F-FET Vt at 48 h after SE (amygdala: −30.2%, p = 0.014), whereas 18F-FDG showed increased glucose uptake 4 and 24 h after SE (hippocampus: + 43.6% and +42.5%, respectively; p < 0.001) returning to baseline levels thereafter. In chronic epileptic animals, we found a reduction in 18F-FET and 18F-FDG in the hippocampus. No correlation was found for 18F-FET or 18F-FDG to microglial activation at seven days post SE. Whereas metabolic alterations do not reflect higher metabolism associated to activated microglia, they might be partially driven by chronic neuronal loss. However, both metabolisms diverge during early epileptogenesis, pointing to amino acid turnover as a possible biomarker and/or therapeutic target for epileptogenesis.