Citrulline and Nonessential Amino Acids Prevent Fructose-Induced Nonalcoholic Fatty Liver Disease in Rats

Jegatheesan, Prasanthi; Beutheu, Stéphanie; Ventura, G.; Nubret, E.; Sarfati, G.; Bergheim, Ina; Bandt, Jean‐Pascal De

doi:10.3945/jn.115.218982

Cited by 39 publications

(55 citation statements)

References 45 publications

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“…There is evidence for citrulline as a key regulator in lipid metabolism, inflammation, and oxidative stress [68], [69], [70], [71]. In addition, studies support its role in skeletal muscle protein metabolism and its trophic effect on the gut [70], [72].…”

Section: Discussionmentioning

confidence: 97%

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Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

Stechemesser

Eder

Wagner

et al. 2017

Molecular Metabolism

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ObjectiveElevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways.MethodsIn a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1) lean, healthy controls (n = 53), (2) MetS without hyperferritinemia (n = 54) and (3) MetS with hyperferritinemia (n = 56). An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach.ResultsSubjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001), HbA1c (p = 0.035) and 1 h glucose in oral glucose tolerance test (p = 0.002) compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites).ConclusionsOur data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.

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Section: Discussionmentioning

confidence: 97%

“…In addition, studies support its role in skeletal muscle protein metabolism and its trophic effect on the gut [70], [72]. Recent findings indicate that citrulline may offer a therapeutic strategy for NAFLD [68], [69]. Citrulline is produced in the urea cycle mainly from ornithine and carbamoyl phosphate [73].…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

Stechemesser

Eder

Wagner

et al. 2017

Molecular Metabolism

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“…That the effect of arginine supplementation depends on prevailing arginine status could only be hypothesized from fragmented data in the literature. Some studies have shown that increasing arginine availability can restore cellular NO production and contribute to regulating the inflammatory process in situations of low plasma arginine concentrations (in diabetic obese rats or fructose-fed rats), reflecting impaired arginine metabolism (50,51). Similarly, there have been reports of improved NO synthesis after arginine supplementation in patients with sickle cell disease during a vasoocclusive crisis, when baseline plasma arginine concentrations are low (46 mmol/L) and characteristic of ''arginine deficiency'' states in other clinical conditions (52,53).…”

Section: Discussionmentioning

confidence: 99%

L-Arginine Supplementation Alleviates Postprandial Endothelial Dysfunction When Baseline Fasting Plasma Arginine Concentration Is Low: A Randomized Controlled Trial in Healthy Overweight Adults with Cardiometabolic Risk Factors

Deveaux

Pham

West

et al. 2016

The Journal of Nutrition

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Supplementation with low-dose SR-arginine alleviates postprandial endothelial dysfunction in healthy HTW adults when the baseline plasma arginine concentration is relatively low. The benefits of arginine supplementation may be linked to a lower ability to mobilize endogenous arginine for nitric oxide synthesis during a postprandial challenge. This trial was registered at clinicaltrials.gov as NCT02354794.

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“…Chronic intake of fructose increases DNL by activating several key transcription factors [12] such as Sterol Response Element Binding Protein 1c (SREBP1c) and Carbohydrate-Responsive Element-Binding Protein (ChREBP) [17,18]. As a consequence, their key target enzymes regulating lipid synthesis, such as Fatty Acid Synthase (FASN) and Acetyl-CoA Carboxylase (ACC), also increase as shown for example in rodents submitted to a 60% high fructose diet for eight weeks [18] or to a western diet where fructose is provided as a 30%-fructose containing beverage for eight weeks [19].…”

Section: Fructose and Hepatic Steatosismentioning

confidence: 99%

“…As a consequence, their key target enzymes regulating lipid synthesis, such as Fatty Acid Synthase (FASN) and Acetyl-CoA Carboxylase (ACC), also increase as shown for example in rodents submitted to a 60% high fructose diet for eight weeks [18] or to a western diet where fructose is provided as a 30%-fructose containing beverage for eight weeks [19]. …”

Section: Fructose and Hepatic Steatosismentioning

confidence: 99%

Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism

2017

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Among various factors, such as an unhealthy diet or a sedentarity lifestyle, excessive fructose consumption is known to favor nonalcoholic fatty liver disease (NAFLD), as fructose is both a substrate and an inducer of hepatic de novo lipogenesis. The present review presents some well-established mechanisms and new clues to better understand the pathophysiology of fructose-induced NAFLD. Beyond its lipogenic effect, fructose intake is also at the onset of hepatic inflammation and cellular stress, such as oxidative and endoplasmic stress, that are key factors contributing to the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Beyond its hepatic effects, this carbohydrate may exert direct and indirect effects at the peripheral level. Excessive fructose consumption is associated, for example, with the release by the liver of several key mediators leading to alterations in the communication between the liver and the gut, muscles, and adipose tissue and to disease aggravation. These multifaceted aspects of fructose properties are in part specific to fructose, but are also shared in part with sucrose and glucose present in energy–dense beverages and foods. All these aspects must be taken into account in the development of new therapeutic strategies and thereby to better prevent NAFLD.

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Citrulline and Nonessential Amino Acids Prevent Fructose-Induced Nonalcoholic Fatty Liver Disease in Rats

Cited by 39 publications

References 45 publications

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

L-Arginine Supplementation Alleviates Postprandial Endothelial Dysfunction When Baseline Fasting Plasma Arginine Concentration Is Low: A Randomized Controlled Trial in Healthy Overweight Adults with Cardiometabolic Risk Factors

Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism

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