Chronic β3-AR stimulation activates distinct thermogenic mechanisms in brown and white adipose tissue and improves systemic metabolism in aged mice.

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle-aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age-related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3-adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18-month-old) C57BL/6JN mice.

The metabolic benefits of thermogenic stimulation are preserved in aging.

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle-aged and older populations, which bear the highest obesity prevalence in the US (approximately 40%), remains uncertain due to age-related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3-adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18-month-old) C57BL/6JN mice.

Effects of improved amino acid balance diet on lysine mammary utilization, whole body protein turnover and muscle protein breakdown on lactating sows.

Background: The study objective was to test the hypothesis that low crude protein (CP) diet with crystalline amino acids (CAA) supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein breakdown. Eighteen lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets (10.80 MJ/kg net energy): control (CON; 19.

MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma.

Neuroblastoma (NB) is a childhood cancer arising from sympatho-adrenal neural crest cells. MYCN amplification is found in half of high-risk NB patients; however, no available therapies directly target MYCN. Using multi-dimensional metabolic profiling in MYCN expression systems and primary patient tumors, we comprehensively characterized the metabolic landscape driven by MYCN in NB.

Correcting for sparsity and interdependence in glycomics by accounting for glycan biosynthesis.

Glycans are fundamental cellular building blocks, involved in many organismal functions. Advances in glycomics are elucidating the essential roles of glycans. Still, it remains challenging to properly analyze large glycomics datasets, since the abundance of each glycan is dependent on many other glycans that share many intermediate biosynthetic steps.

Restoration of the molecular clock is tumor suppressive in neuroblastoma.

MYCN activation is a hallmark of advanced neuroblastoma (NB) and a known master regulator of metabolic reprogramming, favoring NB adaptation to its microenvironment. We found that the expression of the main regulators of the molecular clock loops is profoundly disrupted in MYCN-amplified NB patients, and this disruption independently predicts poor clinical outcome. MYCN induces the expression of clock repressors and downregulates the one of clock activators by directly binding to their promoters.

Prognostic significance of survivin expression in pediatric ewing sarcoma.

Survivin is an inhibitor of apoptosis protein that inhibits caspases and blocks cell death. It is undetectable in most normal adult tissues. High survivin expression has been detected in various tumors and has been correlated with therapy resistance and poor outcome.

Pegylated arginine deiminase depletes plasma arginine but maintains tissue arginine availability in young pigs.

Pegylated arginine deiminase (ADI-PEG20) results in the depletion of arginine with the production of isomolar amounts of citrulline. This citrulline has the potential to be utilized by the citrulline recycling pathway regenerating arginine and sustaining tissue arginine availability. The goal of this research was to test the hypothesis that ADI-PEG20 depletes circulating arginine in pigs but maintains tissue arginine concentration and function, and to characterize the kinetics of citrulline and arginine.

Arginase II Plays a Central Role in the Sexual Dimorphism of Arginine Metabolism in C57BL/6 Mice.

Background: Sex differences in plasma concentration of arginine and arginase activity of different tissues have been reported in mice. In addition, male but not female C57BL/6 mice have a dietary arginine requirement for growth.

Objective: The goal of this research was to test the hypothesis that arginase II is a key factor in the sexual dimorphism of arginine metabolism.

Modeling age-dependent developmental changes in the expression of genes involved in citrulline synthesis using pig enteroids.

Background: Age-dependent changes in the intestinal gene expression of enzymes involved in the metabolism of citrulline and arginine are well characterized. Enteroids, a novel ex-vivo model that recreates the three-dimensional structure of the intestinal crypt-villus unit, have shown to replicate molecular and physiological profiles of the intestinal segment from where they originated ("location memory").

Objective: The present study tested the hypothesis that enteroids recapitulate the developmental changes observed in vivo regarding citrulline production in pigs ("developmental memory").

Reuterin disrupts metabolism and pathogenicity through reactive oxygen species generation.

Antibiotic resistance is one of the world's greatest public health challenges and adjunct probiotic therapies are strategies that could lessen this burden. infection (CDI) is a prime example where adjunct probiotic therapies could decrease disease incidence through prevention. Human-derived is a probiotic that produces the antimicrobial compound reuterin known to prevent colonization of antibiotic-treated fecal microbial communities.

Derangement of Arginine and Related Amino Acids in Children Undergoing Surgery for Congenital Heart Disease With Cardiopulmonary Bypass.

Unlabelled: Arginine is a conditionally essential amino acid, the precursor for nitric oxide and a key factor in cell proliferation, protein synthesis, and energy metabolism. When there is increased demand in the setting of inflammation, ischemia-reperfusion injury, and organ dysfunction, endogenous arginine production falls short, and external supplementation may be necessary. The goal of this study was to assess changes in concentrations of plasma arginine, citrulline, ornithine, glutamine, and plasma arginase in infants and children undergoing surgery for congenital heart disease with cardiopulmonary bypass.

Developmental changes in the utilization of citrulline by neonatal pigs.

Developmental changes in the renal expression and activity of argininosuccinate synthase (ASS1) and argininosuccinate lyase (ASL), enzymes that use citrulline for the production of arginine, have been reported. Thus, the ability of neonates, and especially premature neonates, to produce arginine may be compromised. To determine the utilization of citrulline in vivo, we measured renal expression of and and conducted citrulline compartmental and noncompartmental kinetics using [N]citrulline in pigs of five different ages (from 10 days preterm to 5 wk of age).

A Designer Synbiotic Attenuates Chronic-Binge Ethanol-Induced Gut-Liver Injury in Mice.

Gut dysbiosis and altered short-chain fatty acids are associated with ethanol-induced liver injury. SCFA are fermentation byproducts of the gut microbiota known to have many beneficial biological effects. We tested if a designer synbiotic could protect against ethanol-induced gut-liver injury.

Citrulline Generation Test: What Does It Measure?

Background: The citrulline generation test (CGT) has been proposed as a tool to determine gut function. However, the increase in plasma citrulline concentration that follows a bolus dose of alanyl-glutamine may also result from a reduction in citrulline clearance due to competition with glutamine for transport.

Materials And Methods: A swine model was developed, and stable isotope tracers were used to determine the mechanism behind the increase in plasma citrulline that follows a bolus dose of alanyl-glutamine.

Ex Vivo Enteroids Recapitulate In Vivo Citrulline Production in Mice.

Background: The endogenous production of arginine relies on the synthesis of citrulline by enteral ornithine transcarbamylase (OTC). Mutations in the gene coding for this enzyme are the most frequent cause of urea cycle disorders. There is a lack of correlation between in vivo metabolic function and DNA sequence, transcript abundance, or in vitro enzyme activity.

The Citrulline Recycling Pathway Sustains Cardiovascular Function in Arginine-Depleted Healthy Mice, but Cannot Sustain Nitric Oxide Production during Endotoxin Challenge.

Background: The recycling of citrulline by argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL) is crucial to maintain arginine availability and nitric oxide (NO) production. Pegylated arginine deiminase (ADI-PEG20) is a bacterial enzyme used to deplete circulating arginine.

Objective: The goal of this research was to test the hypothesis that citrulline is able to sustain intracellular arginine availability for NO production in ADI-PEG20 arginine-depleted mice.

A randomized trial to study the comparative efficacy of phenylbutyrate and benzoate on nitrogen excretion and ureagenesis in healthy volunteers.

Purpose: Benzoate and phenylbutyrate are widely used in the treatment of urea cycle disorders, but detailed studies on pharmacokinetics and comparative efficacy on nitrogen excretion are lacking.

Methods: We conducted a randomized, three-arm, crossover trial in healthy volunteers to study pharmacokinetics and comparative efficacy of phenylbutyrate (NaPB; 7.15 g•mBSA•day), benzoate (NaBz; 5.

Role of Melt Curve Analysis in Interpretation of Nutrigenomics' MicroRNA Expression Data.

This article illustrates the importance of melt curve analysis (MCA) in interpretation of mild nutrogenomic micro(mi)RNA expression data, by measuring the magnitude of the expression of key miRNA molecules in stool of healthy human adults as molecular markers, following the intake of Pomegranate juice (PGJ), functional fermented sobya (FS), rich in potential probiotic lactobacilli, or their combination. Total small RNA was isolated from stool of 25 volunteers before and following a three-week dietary intervention trial. Expression of 88 miRNA genes was evaluated using Qiagen's 96 well plate RT miRNA qPCR arrays.

Precursors of hexoneogenesis within the human mammary gland.

The human mammary gland is capable of de novo synthesis of glucose and galactose (hexoneogenesis); however, the carbon source is incompletely understood. In this study, we investigated the role of acetate, glutamine, lactate and glycerol as potential carbon sources for hexoneogenesis. Healthy breastfeeding women were studied following a 24-h fast on two occasions separated by 1-3 wk.

Comparative analyses of lung transcriptomes in patients with alveolar capillary dysplasia with misalignment of pulmonary veins and in foxf1 heterozygous knockout mice.

Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV) is a developmental disorder of the lungs, primarily affecting their vasculature. FOXF1 haploinsufficiency due to heterozygous genomic deletions and point mutations have been reported in most patients with ACDMPV. The majority of mice with heterozygous loss-of-function of Foxf1 exhibit neonatal lethality with evidence of pulmonary hemorrhage in some of them.

De novo synthesis of milk triglycerides in humans.

Unlabelled: Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans.

Objective: To test the hypothesis that the incorporation of (13)C carbons from [U-(13)C]glucose into fatty acids (FA) and glycerol in triglycerides (TG) will be greater: 1) in milk than plasma TG, 2) during a high-carbohydrate (H-CHO) diet than high-fat (H-FAT) diet, and 3) during feeding than fasting. Seven healthy, lactating women were studied on two isocaloric, isonitrogenous diets.