Dose-dependent beneficial effects of citrulline supplementation in short bowel syndrome in rats

Filippi, Jérôme; Rubio, Andres J.; Lasserre, Virgine; Maccario, Jean; Walrand, S; Neveux, N.; Plénier, S. Le; Hébuterne, Xavier; Cynober, Luc; Moinard, Christophe

doi:10.1016/j.nut.2020.111118

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…This suggests that HS may influence the mTOR signaling in a temperature-dependent manner. Additionally, citrulline can regulate muscle protein synthesis via the mTORC1 signaling pathway and activation of its downstream effectors, S6K1 and 4E-BP1 ( Le Plenier et al, 2012 ; Goron et al, 2017 ; Le Plénier et al, 2017 ; Breuillard et al, 2019 ; Filippi et al, 2021 ). Therefore, the lack of significant changes in mTOR’s upstream and downstream targets suggests other possible routes for its activation since it is a key metabolic sensor involved in multiple biological activities.…”

Section: Discussionmentioning

confidence: 99%

Dietary L-citrulline modulates the growth performance, amino acid profile, and the growth hormone/insulin-like growth factor axis in broilers exposed to high temperature

et al. 2022

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Heat stress adversely affects the growth performance, muscle development, and protein metabolism in poultry. l-Citrulline (L-Cit), is a non-essential amino acid that is known to stimulate muscle protein synthesis under stress conditions. This study investigated whether L-Cit could influence the growth performance, amino acid profile, and protein metabolism in broilers exposed to high ambient temperature. In a 2 × 2 factorial arrangement, Arbor acre broilers (288 chickens) were fed with basal diet (CON) or 1% L-Cit supplemented diet and later subjected to either thermoneutral (TNZ: 24°C, 24 h/d) or heat stress (HS: 35°C for 8 h/d) environment for 21 days. The results showed that L-Cit diet promoted the body weight and body weight gain of broilers higher than the CON diet, and it further alleviated HS suppression of body weight and feed intake at certain periods (p < 0.05). Plasma urea, uric acid, glucose, and total cholesterol were elevated during HS, whereas, the triglyceride content was decreased (p < 0.05). Serum amino acids including citrulline, alanine, aspartate, and taurine were decreased by HS. L-Cit supplementation restored the citrulline level and alleviated HS induction of 3-methylhistidine (p < 0.05). L-Cit supplementation increased the plasma growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentration, as well as the GH concentration in the breast muscle (p < 0.05). The mRNA expression showed that HS elicited tissue-specific responses by upregulating some growth factors in the breast muscle, but downregulated the GH receptor, GH binding protein, and IGF-1 expression in the hypothalamus. L-Cit supplementation upregulated the GHRH and IGFBP2 expression in the hypothalamus. L-Cit also upregulated the expression of IGF-1R and IGFBP2 in the breast muscle of HS broilers. The total mTOR protein level in the breast muscle of HS broilers was also increased by L-Cit diet (p < 0.05). Therefore, this study demonstrated that HS negatively affected the growth performance of broilers and dysregulated the expression of growth factors related to protein metabolism. Contrarily, L-Cit promoted the growth responses of broilers via its stimulation of circulating GH/IGF-1 concentration. To certain extents, L-Cit supplementation elicited protective effects on the growth performance of HS broilers by diminishing protein catabolism.

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Section: Discussionmentioning

confidence: 99%

Dietary L-citrulline modulates the growth performance, amino acid profile, and the growth hormone/insulin-like growth factor axis in broilers exposed to high temperature

et al. 2022

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“…Coherently, parenteral nutrition supplemented with SCFAs and, in particular, butyrate at physiological concentrations, is described to improve structural and metabolic adaptation (i.e. increased villus height, number of crypt cells and plasma GLP-2 concentrations) in the small intestine, accelerates adaptation and potentially shortens the period of full adaptation, in a SBS piglet model (Jeppesen et al 2000 , Bartholome et al 2004 , Filippi et al 2021 ). Furthermore, after reinfusing proximal jejunostomy output into the distal part of the small intestine Liu et al ( 2016 ) observed a shorter parenteral nutrition period, protected integrity of the intestinal mucosa and increased nutrient absorption, in particular when the ileocecal valve was preserved.…”

Section: Disruption Of Small Intestinal Homeostasis In Nutrient Balancementioning

confidence: 99%

The small intestine: dining table of host–microbiota meetings

Delbaere

Roegiers

Bron

et al. 2023

FEMS Microbiology Reviews

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Growing evidence suggests the importance of the small intestinal bacteria in the diet-host-microbiota dialogue in various facets of health and disease. Yet, this body site is still poorly explored and its ecology and mechanisms of interaction with the host are just starting to be unraveled. In this review, we describe the current knowledge on the small intestinal ecology, its composition and diversity, and how the intestinal bacteria in homeostatic conditions participate in nutrient digestion and absorption. We illustrate the importance of a controlled bacterial density and of the preservation of absorptive surface for the host's nutritional status. In particular, we discuss these aspects of the small intestinal environment in the framework of two disease conditions, namely small intestinal bacterial overgrowth (SIBO) and short bowel syndrome (SBS). We also detail in vivo, ex vivo and in vitro models developed to simulate the small intestinal environment, some applied for (diet-)host-bacteria interaction studies. Lastly, we highlight recent technological, medical and scientific advances applicable to investigate this complex and yet understudied body environment to broaden our knowledge in support of further progress in the medical practice, and to proceed towards the integration of the (small)intestinal bacteria in personalized therapeutic approaches.

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“…[20,21] Increasing dietary L-cit levels has beneficial effects on animal intestinal development, function, and immune defense. [22,23] Moreover, L-cit can also regulate the gut microbiota and has prebiotic properties. [24,25] However, the effects of L-cit on iron overload-induced damage of mitochondria in intestine remain to be examined.…”

Section: Introductionmentioning

confidence: 99%

L‐Citrulline Ameliorates Iron Metabolism and Mitochondrial Quality Control via Activating AMPK Pathway in Intestine and Improves Microbiota in Mice with Iron Overload

Zhao,

Gao,

Chen

et al. 2024

Molecular Nutrition Food Res

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ScopeOxidative stress caused by iron overload tends to result in intestinal mucosal barrier dysfunction and intestinal microbiota imbalance. As a neutral and nonprotein amino acid, L‐Citrulline (L‐cit) has been implicated in antioxidant and mitochondrial amelioration properties. This study investigates whether L‐cit can alleviate iron overload‐induced intestinal injury and explores the underlying mechanisms.Methods and resultsC57BL/6J mice are intraperitoneally injected with iron dextran, then gavaged with different dose of L‐cit for 2 weeks. L‐cit treatment significantly alleviates intestine pathological injury, oxidative stress, ATP level, and mitochondrial respiratory chain complex activities, accompanied by ameliorating mitochondrial quality control. L‐cit‐mediated protection is associated with the upregulation of Glutathione Peroxidase 4 (GPX4) expression, inhibition Nuclear Receptor Coactivator 4 (NCOA4)‐mediated ferritinophagy and ferroptosis, and improvement of gut microbiota. To investigate the underlying molecular mechanisms, Intestinal Porcine Epithelial Cell line‐J2 (IPEC‐J2) cells are treated with L‐cit or AMP‐activated Protein Kinase (AMPK) inhibitor. AMPK signaling has been activated by L‐cit. Notably, Compound C abolishes L‐cit's protection on intestinal barrier, mitochondrial function, and antioxidative capacity in IPEC‐J2 cells.ConclusionL‐cit may restrain ferritinophagy and ferroptosis to regulate iron metabolism, and induce AMPK pathway activation, which contributes to exert antioxidation, ameliorate iron metabolism and mitochondrial quality control, and improve intestinal microbiota. L‐cit is a promising therapeutic strategy for iron overload‐induced intestinal injury.

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Dose-dependent beneficial effects of citrulline supplementation in short bowel syndrome in rats

Cited by 7 publications

References 27 publications

Dietary L-citrulline modulates the growth performance, amino acid profile, and the growth hormone/insulin-like growth factor axis in broilers exposed to high temperature

Dietary L-citrulline modulates the growth performance, amino acid profile, and the growth hormone/insulin-like growth factor axis in broilers exposed to high temperature

The small intestine: dining table of host–microbiota meetings

L‐Citrulline Ameliorates Iron Metabolism and Mitochondrial Quality Control via Activating AMPK Pathway in Intestine and Improves Microbiota in Mice with Iron Overload

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