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(a) Comparison of mean ± SEM villus height in the morning and evening, with or without food. Representative histologic sections taken at 200× magnification for mice (b) fed freely, morning harvest, (c) fed freely, evening harvest, (d) fasted, morning harvest, and (e) fasted, evening harvest.
Source publication
Background
Plasma citrulline is a nonessential amino acid synthesized almost exclusively by enterocytes of the small intestine. Correlation between post-operative plasma citrulline levels and remnant small bowel mass and function has led to its use as a simple biomarker of functional intestinal mass in adults and children, with a proposed prognosti...
Contexts in source publication
Context 1
... in enterocyte mass, or quantity, are commonly associated with changes in villus height (VH). Thus, as an estimate of enterocyte mass between mice, VH was measured spanning the entire small intestine. There was no significant difference in VH between all four experimental groups (Fig. 2a-e). The mean ± SEM VHs were as follows: am fasted VH = 263.6 ± 8.123 µm; pm fasted VH = 260.3 ± 7.665; am fed VH = 258.4 ± 11.52; pm fed VH = 284.6 ± 14.21 (P > 0.05 for all ...
Context 2
... in enterocyte mass, or quantity, are commonly associated with changes in villus height (VH). Thus, as an estimate of enterocyte mass between mice, VH was measured spanning the entire small intestine. There was no significant difference in VH between all four experimental groups (Fig. 2a-e). The mean ± SEM VHs were as follows: am fasted VH = 263.6 ± 8.123 µm; pm fasted VH = 260.3 ± 7.665; am fed VH = 258.4 ± 11.52; pm fed VH = 284.6 ± 14.21 (P > 0.05 for all ...
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Citations
... Serum biomarkers are widely used in disease detection (Chen et al., 2022;Mirshafiei et al., 2022). Serum citrulline levels are associated with food intake in mice (Park et al., 2019). The levels of total amino acids in serum showed no significant difference between treatments. ...
Germ cell loss is a crucial biological event during germ cell development. The number of female germ cells determines the reproductive performance and egg production of hens. Various intrinsic and extrinsic factors affect germ cell loss, such as germ cell nest breakdown in early life and nutritional deficiencies during daily husbandry. Here, we examined the effect of fasting on the germ cell number of chicks. The results showed that 72 h fasting resulted in a higher germ cell loss than that by 24 h fasting in chicks. The RNA-seq analysis revealed that the genes of ribosome pathway were down-regulated and the biological processes of protein processing in endoplasmic reticulum were inhibited in starved chicks. Furthermore, in female chicks treated with 72 h fasting, the qPCR of ovaries showed down-regulation of ribosome-related genes, and transmission electron microscopy imaging of ovaries showed fewer ribosomes. The blood biochemical indices indicated that 72 h fasting reduced the liver functions and affected the glucose metabolism, lipid metabolites and ion metabolites. In summary, the present results concluded negative impacts on the germ cell pool by prolonged fasting in the early life of chicks and manifested that adequate management should be cared for fasted time for breeding.
... 24,35 In an experimental study by Park et al., serial measurements reduced the potential confounding effect of circadian variation and fluctuations in citrulline levels. 37 Our study did not reveal any correlation between citrulline levels and clinical parameters such as estimated glomerular filtration rate (eGFR) or C-reactive protein (CRP) levels. This is surprising because kidney disorders and enhanced inflammatory processes may induce changes in citrulline levels. ...
Background:
Cardiovascular disease (CVD) is associated with intestinal barrier dysfunction and increased intestinal permeability. Increased intestinal permeability to gut microbial metabolites may accelerate the progression of CVD. Plasma citrulline levels are a marker of functional enterocyte mass, and reduced citrulline levels indicate intestinal epithelial damage. Citrulline was reported as a useful prognostic marker in critically ill patients. However, data are lacking on the association of citrulline with long-term mortality in patients with CVD and with the levels of trimethylamine N-oxide (TMAO), a microbiota-derived metabolite which has been implicated in the pathogenesis of CVD.
Objectives:
To assess the effect of citrulline levels, a marker of intestinal barrier disruption, on long-term mortality in patients with CVD. Moreover, the relationship between the concentrations of 2 biomarkers - citrulline and TMAO - was assessed.
Material and methods:
Serum citrulline levels were retrospectively assessed in 1036 consecutive patients with CVD (median age: 62 years; 61% men) hospitalized between 2013 and 2015. Associations of citrulline levels with 5-year mortality rates as well as anthropometric and biochemical parameters were evaluated for the entire study group and in subgroups of patients with acute coronary syndrome (ACS), chronic coronary syndrome, chronic heart failure (chronic HF), and atrial fibrillation (AF). Correlations between serum citrulline and TMAO levels were assessed.
Results:
The median citrulline level in the study population was 22.5 μM (interquartile range (IQR): 17.8-27.9). Citrulline levels were not associated with 5-year mortality in patients with CVD (hazard ratio (HR) = 0.99; 95% confidence interval (95% CI): 0.97-1.00; p = 0.49). Median citrulline levels differed significantly between deceased patients and survivors at 5 years in patients with ACS (p = 0.025). There were no significant correlations between citrulline and TMAO levels (Kendall's tau = 0.027).
Conclusions:
Decreasing citrulline levels do not predict long-term mortality of hospitalized patients with CVD. Moreover, they are not associated with the serum levels of TMAO in these patients.
... Serum citrulline, a marker of functional enterocyte mass [51,52], was measured calorimetrically. Blood samples were obtained via standard retrobulbar technique on day 0, 14, and 28. ...
Previous work demonstrated enhanced enterocyte proliferation and mucosal growth in gnotobiotic mice, suggesting that intestinal flora participate in mucosal homeostasis. Furthermore, broad-spectrum enteral antibiotics are known to induce near germ-free (GF) conditions in mice with conventional flora (CONV). We hypothesized that inducing near GF conditions with broad-spectrum enteral antibiotics would cause ordered small intestinal mucosal growth in CONV mice but would have no effect in GF mice with no inherent microbiome. C57BL/6J CONV and GF mice received either an antibiotic solution (Ampicillin, Ciprofloxacin, Metronidazole, Vancomycin, Meropenem) or a vehicle alone. After treatment, small intestinal villus height (VH), crypt depth (CD), mucosal surface area (MSA), crypt proliferation index (CPI), apoptosis, and villus and crypt cell types were assessed. Antibiotic-treated CONV (Abx-CONV) mice had taller villi, deeper crypts, increased CPI, increased apoptosis, and greater MSA compared to vehicle-treated CONV mice. Minor differences were noted in enterocyte and enterochromaffin cell proportions between groups, but goblet and Paneth cell proportions were unchanged in Abx-CONV mice compared to vehicle-treated CONV mice (p>0.05). Antibiotics caused no significant changes in VH or MSA in GF mice when compared to vehicle-treated GF mice (p>0.05). Enteral administration of broad-spectrum antibiotics to mice with a conventional microbiome stimulates ordered small intestinal mucosal growth. Mucosal growth was not seen in germ-free mice treated with antibiotics, implying that intestinal mucosal growth is associated with change in the microbiome in this model.
... Citrulline is a nonessential amino acid synthesized almost exclusively by enterocytes of the small intestine. Serum citrulline levels have previously been linked to changes in food intake in mice 49 and human www.nature.com/scientificreports/ studies 50,51 . ...
... studies 50,51 . Notably, in fasted mice, significantly higher levels of serum citrulline were observed in the morning compared to the evening 49 . In addition, increased plasma citrulline in mice is associated with diet-induced obesity and may predict the development of the metabolic syndrome 52 . ...
Antipsychotic drugs (AP) are used to treat a multitude of psychiatric conditions including schizophrenia and bipolar disorder. However, APs also have metabolic side effects including increased food intake and body weight, but the underlying mechanisms remain unknown. We previously reported that minocycline (MINO) co-treatment abrogates olanzapine (OLZ)-induced hyperphagia and weight gain in mice. Using this model, we investigated the changes in the pharmacometabolome in the plasma and hypothalamus associated with OLZ-induced hyperphagia and weight gain. Female C57BL/6 mice were divided into groups and fed either i) control, CON (45% fat diet) ii) CON + MINO, iii) OLZ (45% fat diet with OLZ), iv) OLZ + MINO. We identified one hypothalamic metabolite indoxylsulfuric acid and 389 plasma metabolites (including 19 known metabolites) that were specifically associated with AP-induced hyperphagia and weight gain in mice. We found that plasma citrulline, tricosenoic acid, docosadienoic acid and palmitoleic acid were increased while serine, asparagine and arachidonic acid and its derivatives were decreased in response to OLZ. These changes were specifically blocked by co-treatment with MINO. These pharmacometabolomic profiles associated with AP-induced hyperphagia and weight gain provide candidate biomarkers and mechanistic insights related to the metabolic side effects of these widely used drugs.
... These results indicate that plasma citrulline is affected by experimental conditions such as anesthesia and feeding. In a study by Park et al 93 it was found that serum citrulline levels in mice showed diurnal changes and fluctuations related to food intake with no significant simultaneous change in the intestinal cell mass. Serum citrulline levels in fed mice did not change daily, while in fasted mice it was significantly higher in the morning than at night. ...
Radiation damage assessment of the small intestine is important in nuclear accidents or routine radiotherapy of abdominal tumors. This article reviews the clinical symptoms and molecular mechanisms of radiation-induced small intestinal damage and summarizes recent research on biomarkers of such damage. Citrulline is the most promising biomarker for the evaluation of radiation-induced small intestinal damage caused by radiotherapy and nuclear accidents. This article also summarizes the factors influencing plasma citrulline measurement investigated in the latest research, as well as new findings on the concentration of citrulline in saliva and urine after different types of radiation.
... The Citrulline Assay Kit (CAK) is a simple colorimetric assay that measures the amount of total citrulline present in biological samples such as cells, tissue, plasma serum, or urine samples [36][37][38]. Watermelon tissue sample extracts were treated with sodium dodecyl sulfate (SDS) and proteinase K to release free citrulline residues, followed by the addition of assay reagents (assay reagents A and B). The reaction of assay reagents with the released free citrulline at 95 • C produces chromophore that absorbs UV light at 540-560 nm. ...
Watermelon (Citrullus lanatus) is a non-seasonal, economically important, cucurbit cultivated throughout the world, with Asia as a continent contributing the most. As part of the effort to diversify watermelon genetic resources in the already cultivated group, this study was devoted to providing baseline data on morphological quality traits and health-beneficial phytonutrients of watermelon germplasm collections, thereby promoting watermelon research and cultivation programs. To this end, we reported morphological traits, citrulline, and arginine levels of watermelon genetic resources obtained from the gene bank of Agrobiodiversity Center, Republic of Korea, and discussed the relationships between each. Diverse characteristics were observed among many of the traits, but most of the genetic resources (>90%) were either red or pink-fleshed. Korean originated fruits contained intermediate levels of soluble solid content (SSC) while the USA, Russian, Tajikistan, Turkmenistan, Taiwan, and Uruguay originated fruits had generally the highest levels of soluble solids. The citrulline and arginine contents determined using the High Performance Liquid Chromatography (HPLC) method ranged from 6.9 to 52.1 mg/g (average, 27.3 mg/g) and 1.8 to 21.3 mg/g (average, 9.8 mg/g), respectively. The citrulline content determined using the Citrulline Assay Kit ranged from 6.5 to 42.8 mg/g (average, 27.0 mg/g). Resources with high citrulline and arginine levels contained low SSC, whereas red- and pink-colored flesh samples had less citrulline compared to yellow and orange.
