Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice

Urasaki, Yasuyo; Pizzorno, Giuseppe; Le, Thuc T.

doi:10.1371/journal.pone.0146994

Cited by 59 publications

(57 citation statements)

References 37 publications

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“…We previously reported the existence of a UDP-uridine loop in which hypothalamic UDP contents are increased in obesity as a direct consequence of elevated uridine supply from the periphery (Steculorum et al, 2015b). Consistent with this model, chronic uridine supplementation in mice leads to glucose intolerance associated with decreased insulin signaling in liver and increase hepatic gluconeogenesis (Urasaki et al, 2016). These data in conjunction with the results of the present study suggest that increased hypothalamic UDP levels, as a result of elevated peripheral supply of uridine, directly act on AgRP neurons to control hepatic insulin sensitivity and to deteriorate systemic insulin sensitivity and glucose homeostasis.…”

Section: Discussionsupporting

confidence: 54%

Inhibition of P2Y6 Signaling in AgRP Neurons Reduces Food Intake and Improves Systemic Insulin Sensitivity in Obesity

et al. 2017

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Uridine-diphosphate (UDP) and its receptor P2Y6 have recently been identified as regulators of AgRP neurons. UDP promotes feeding via activation of P2Y6 receptors on AgRP neurons, and hypothalamic UDP concentrations are increased in obesity. However, it remained unresolved whether inhibition of P2Y6 signaling pharmacologically, globally, or restricted to AgRP neurons can improve obesity-associated metabolic dysfunctions. Here, we demonstrate that central injection of UDP acutely promotes feeding in diet-induced obese mice and that acute pharmacological blocking of CNS P2Y6 receptors reduces food intake. Importantly, mice with AgRP-neuron-restricted inactivation of P2Y6 exhibit reduced food intake and fat mass as well as improved systemic insulin sensitivity with improved insulin action in liver. Our results reveal that P2Y6 signaling in AgRP neurons is involved in the onset of obesity-associated hyperphagia and systemic insulin resistance. Collectively, these experiments define P2Y6 as a potential target to pharmacologically restrict both feeding and systemic insulin resistance in obesity.

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Section: Discussionsupporting

confidence: 54%

Inhibition of P2Y6 Signaling in AgRP Neurons Reduces Food Intake and Improves Systemic Insulin Sensitivity in Obesity

et al. 2017

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“…Uridine, a necessary pyrimidine nucleotide for RNA synthesis, can be synthesized de novo in mammals [1][2][3]. Uridine has been widely used in reducing cytotoxicity [4] and improving neurophysiological functions [5,6].…”

Section: Introductionmentioning

confidence: 99%

Uridine Metabolism and Its Role in Glucose, Lipid, and Amino Acid Homeostasis

Zhang

Guo

Xie

et al. 2020

BioMed Research International

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Pyrimidine nucleoside uridine plays a critical role in maintaining cellular function and energy metabolism. In addition to its role in nucleoside synthesis, uridine and its derivatives contribute to reduction of cytotoxicity and suppression of drug-induced hepatic steatosis. Uridine is mostly present in blood and cerebrospinal fluid, where it contributes to the maintenance of basic cellular functions affected by UPase enzyme activity, feeding habits, and ATP depletion. Uridine metabolism depends on three stages: de novo synthesis, salvage synthesis pathway and catabolism, and homeostasis, which is tightly relating to glucose homeostasis and lipid and amino acid metabolism. This review is devoted to uridine metabolism and its role in glucose, lipid, and amino acid homeostasis.

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“…As the metabolic product of UMP, uridine (UR) exerts restorative functions in tissues under stress . It has been reported that supplementation with fish oil and UR supports the intestinal physical barrier via up‐regulating of the ZO‐1 level .…”

Section: Introductionmentioning

confidence: 99%

“…10 As the metabolic product of UMP, uridine (UR) exerts restorative functions in tissues under stress. 11 It has been reported that supplementation with fish oil and UR supports the intestinal physical barrier via up-regulating of the ZO-1 level. 12 Intra-colonic administration of UR effectively prevented the development and progression of the dextran sulfate sodium (DSS) induced colitis symptoms in mice.…”

Section: Introductionmentioning

confidence: 99%

Dietary supplement with nucleotides in the form of uridine monophosphate or uridine stimulate intestinal development and promote nucleotide transport in weaned piglets

Xie

Wang

et al. 2019

J Sci Food Agric

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BACKGROUND Nucleotides are key constituents of milk, where they are utilized in cell replication, although there are limited studies for weaned piglets. This study evaluated the effects of uridine monophosphate (UMP) with uridine (UR) feed supplementation on the intestinal development and nucleotide transport in weaned piglets. RESULTS Supplementation with UMP significantly increased (P < 0.05) plasma glucose, and UR supplementation significantly reduced (0.05 < P < 0.10) the plasma total cholesterol (TC) of piglets when compared with that of the control group, although non‐significant difference (P > 0.05) in growth performance was observed among three groups. Piglets fed supplementary UR exhibited greater (P < 0.05) crypt depth in the duodenum and ileum when compared with those in the supplementary UMP and control groups. Real‐time quantitative polymerase chain reaction (RT‐qPCR) results revealed that UR supplementation increased (P < 0.05) the relative mRNA levels of genes encoding the transmembrane proteins ZO‐1 and occludin in the duodenum mucosa, and ZO‐1 in the jejunum mucosa (P < 0.05). Similarly, UR supplementation increased (P < 0.05) expression of solute carriers SLC28A1 and SLC29A1 in the duodenum mucosa. Conversely, claudin‐1 expression in the duodenum mucosa was inhibited (P < 0.05) by dietary supplementation with UMP or UR. CONCLUSION Collectively, our data indicated that dietary supplementation with UMP or UR was conducive to stimulating intestinal development and promoting nucleotide transport in weaned piglets. © 2019 Society of Chemical Industry

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Chronic Uridine Administration Induces Fatty Liver and Pre-Diabetic Conditions in Mice

Cited by 59 publications

References 37 publications

Inhibition of P2Y6 Signaling in AgRP Neurons Reduces Food Intake and Improves Systemic Insulin Sensitivity in Obesity

Inhibition of P2Y6 Signaling in AgRP Neurons Reduces Food Intake and Improves Systemic Insulin Sensitivity in Obesity

Uridine Metabolism and Its Role in Glucose, Lipid, and Amino Acid Homeostasis

Dietary supplement with nucleotides in the form of uridine monophosphate or uridine stimulate intestinal development and promote nucleotide transport in weaned piglets

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