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

BACKGROUND: Fructose induces nonalcoholic fatty liver disease (NAFLD). Citrulline (Cit) may exert a beneficial effect on steatosis. OBJECTIVE: We compared the effects of Cit and an isonitrogenous mixture of nonessential amino acids (NEAAs) on fructose-induced NAFLD. METHODS: Twenty-two male Sprague Dawley rats were randomly assigned into 4 groups (n = 4-6) to receive for 8 wk a 60% fructose diet, either alone or supplemented with Cit (1 g · kg(-1) · d(-1)), or an isonitrogenous amount of NEAAs, or the same NEAA-supplemented diet with starch and maltodextrin instead of fructose (controls). Nutritional and metabolic status, liver function, and expression of genes of hepatic lipid metabolism were determined. RESULTS: Compared with controls, fructose led to NAFLD with significantly higher visceral fat mass (128%), lower lean body mass (-7%), insulin resistance (135%), increased plasma triglycerides (TGs; 67%), and altered plasma amino acid concentrations with decreased Arg bioavailability (-27%). This was corrected by both NEAA and Cit supplementation. Fructose caused a 2-fold increase in the gene expression of fatty acid synthase (Fas) and 70% and 90% decreases in that of carnitine palmitoyl-transferase 1a and microsomal TG transfer protein via a nearly 10-fold higher gene expression of sterol regulatory element-binding protein-1c (Srebp1c) and carbohydrate-responsive element-binding protein (Chrebp), and a 90% lower gene expression of peroxisome proliferator-activated receptor α (Ppara). NEAA or Cit supplementation led to a Ppara gene expression similar to controls and decreased those of Srebp1c and Chrebp in the liver by 50-60%. Only Cit led to Fas gene expression and Arg bioavailability similar to controls. CONCLUSION: In our rat model, Cit and NEAAs effectively prevented fructose-induced NAFLD. On the basis of literature data and our findings, we propose that NEAAs may exert their effects specifically on the liver, whereas Cit presumably acts at both the hepatic and whole-body level, in part via improved peripheral Arg metabolism.

Early chloride intake does not parallel that of sodium in extremely-low-birth-weight infants and may impair neonatal outcomes.

BACKGROUND AND OBJECTIVE: Accurate data on the optimal chloride (Cl) intake in premature infants are scarce. The aim of the present study was to describe Cl intakes in the first 10 days of life and to assess the relations between high Cl intakes and corrected serum Cl level or markers of severe acidosis in infants <28 weeks' gestation. METHODS: Retrospective cohort study including all of the infants <28 weeks admitted to the neonatal intensive care unit during a 3-year period and cared for from birth until day 10 or more. RESULTS: Fifty-six infants were included. Cumulative total Cl intakes reached 9.6 ± 3.7 mmol/kg at day 3 and 49.2 ± 13.5 mmol/kg at day 10. Inadvertent intakes (from intravenous fluids other than parenteral nutrition) represented on average 70% of total Cl intakes in the first 3 days. Difference between Cl and sodium intakes reached 7.8 ± 4.8 mmol/kg at day 10 and mainly originated from parenteral nutrition. By multivariate analysis, cumulative Cl intake >10 mmol/kg during the first 3 days was an independent risk factor of base excess <-10 mmol/L. Cumulative Cl intake >45 mmol/kg during the first 10 days was an independent risk factor of corrected chloremia >115 mmol/L and of base excess <-10 mmol/L. CONCLUSIONS: Cumulative Cl intake >10 mmol/kg during the first 3 days (ie, 3.3 mmol · kg (-1) · day(-1) on average) and >45 mmol/kg during the first 10 days (ie, 4.5 mmol · kg (-1) · day(-1) on average) may have unwanted metabolic consequences and should be avoided. Imbalance between electrolytes provided by the parenteral nutrition solution need to be detected and corrected.

Influence of an ω3-fatty acid-enriched enteral diet with and without added glutamine on the metabolic response to injury in a rat model of prolonged acute catabolism.

OBJECTIVE: In critically ill patients, acute injury alters gut function, causing greater risk for sepsis and malnutrition. Peptide-enriched diets may promote nitrogen absorption, whereas ω3-enriched diets reduce alterations in gut barrier function. The aim of this study was to assess the effectiveness of a peptide- and ω3-enriched diet on the metabolic response to injury and the gut barrier function in a model of prolonged catabolism in the rat. Given the intestinal trophic effect of glutamine, we tested for a synergistic effect of glutamine. METHODS: We randomized 40 male Sprague-Dawley rats (250 g) into four groups to enterally receive a standard high-protein diet (S), or a peptide- and ω3-enriched diet either alone (IMN) or supplemented with glutamine and alanine supplied as dipeptide (DIP) or as free amino acids (AAs) for 4 d. Metabolic response to injury was induced by turpentine injections on days 1 and 3. At sacrifice, nutritional and inflammatory biomarkers and intestinal and liver function were assessed. RESULTS: Weight gain (+45-62%) and nitrogen balance (+33-56%) were significantly higher in all groups than in the S group. In jejunal mucosa, total glutathione was significantly higher (+20-30%) and myeloperoxidase activity significantly lower in all groups compared with the S group. Hepatic triacylglycerol content was significantly lower in the AA (0.30 ± 0.04 µM/g) and DIP (0.43 ± 0.08 µM/g) groups than in the S group (0.71 ± 0.08 µM/g). CONCLUSIONS: In this model of prolonged catabolism, compared with a standard diet, a peptide- and ω3-enriched diet improved metabolic response to injury, with better nitrogen balance and weight recovery, and decreased intestinal myeloperoxidase activity. Only marginal additional effects of glutamine supplementation were observed with decreased hepatic fat content.

Effect of specific amino acids on hepatic lipid metabolism in fructose-induced non-alcoholic fatty liver disease.

BACKGROUND & AIM: Fructose diets have been shown to induce insulin resistance and to alter liver metabolism and gut barrier function, ultimately leading to non-alcoholic fatty liver disease. Citrulline, Glutamine and Arginine may improve insulin sensitivity and have beneficial effects on gut trophicity. Our aim was to evaluate their effects on liver and gut functions in a rat model of fructose-induced non-alcoholic fatty liver disease. METHODS: Male Sprague-Dawley rats (n = 58) received a 4-week fructose (60%) diet or standard chow with or without Citrulline (0.15 g/d) or an isomolar amount of Arginine or Glutamine. All diets were made isonitrogenous by addition of non-essential amino acids. At week 4, nutritional and metabolic status (plasma glucose, insulin, cholesterol, triglycerides and amino acids, net intestinal absorption) was determined; steatosis (hepatic triglycerides content, histological examination) and hepatic function (plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin) were assessed; and gut barrier integrity (myeloperoxidase activity, portal endotoxemia, tight junction protein expression and localization) and intestinal and hepatic inflammation were evaluated. We also assessed diets effects on caecal microbiota. RESULTS: In these experimental isonitrogenous fructose diet conditions, fructose led to steatosis with dyslipidemia but without altering glucose homeostasis, liver function or gut permeability. Fructose significantly decreased Bifidobacterium and Lactobacillus and tended to increase endotoxemia. Arginine and Glutamine supplements were ineffective but Citrulline supplementation prevented hypertriglyceridemia and attenuated liver fat accumulation. CONCLUSION: While nitrogen supply alone can attenuate fructose-induced non-alcoholic fatty liver disease, Citrulline appears to act directly on hepatic lipid metabolism by partially preventing hypertriglyceridemia and steatosis.

Diagnosis of Iron Deficiency in Inflammatory Bowel Disease by Transferrin Receptor-Ferritin Index.

Iron deficiency is common in patients with inflammatory bowel disease (IBD), but can be difficult to diagnose in the presence of inflammation because ferritin is an acute phase reactant. The transferrin receptor-ferritin index (TfR-F) has a high sensitivity and specificity for iron deficiency diagnosis in chronic diseases. The diagnostic efficacy of TfR-F is little known in patients with IBD. The aim of the study was to assess the added value of TfR-F to iron deficiency diagnosis in a prospective cohort of patients with IBD.Consecutive IBD patients were prospectively enrolled. Patients were excluded in case of blood transfusion, iron supplementation, or lack of consent. IBD activity was assessed on markers of inflammation (C-reactive protein, endoscopy, fecal calprotectin). Hemoglobin, ferritin, vitamin B9 and B12, Lactate dehydrogenase, haptoglobin, and soluble transferrin receptor (sTfR) were assayed. TfR-F was calculated as the ratio sTfR/log ferritin. Iron deficiency was defined by ferritin <30 ng/mL or TfR-F >2 in the presence of inflammation.One-hundred fifty patients with median age 38 years (16-78) and Crohn disease (n = 105), ulcerative colitis (n = 43), or unclassified colitis (n = 2) were included. Active disease was identified in 45.3%. Anemia was diagnosed in 28%. Thirty-six patients (24%) had ferritin <30 ng/mL. Thirty-two patients (21.3%) had ferritin levels from 30 to 100 ng/ml and inflammation: 2 had vitamin B12 deficiency excluding TfR-F analysis, 13 of 30 (43.3%) had TfR-F >2. Overall, iron deficiency was diagnosed in 32.7% of the patients.TfR-F in addition to ferritin <30 ng/mL criterion increased by 36% diagnosis rates of iron deficiency. TfR-F appeared as a useful biomarker that could help physicians to diagnose true iron deficiency in patients with active IBD.