Effects of Long‐term Parenteral Nutrition on Serum Lipids, Plant Sterols, Cholesterol Metabolism, and Liver Histology in Pediatric Intestinal Failure

Kurvinen, Annika; Nissinen, Markku; Gylling, Helena; Miettinen, Tatu A.; Lampela, Hanna; Koivusalo, Antti; Rintala, Risto; Pakarinen, Mikko P.

doi:10.1097/mpg.0b013e3182212130

Cited by 58 publications

(75 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These fi ndings suggest that IL-induced intrahepatic accumulation of conjugated bile acid is associated with biliary injury, which may precede hepatocellular injury. Direct examination of the liver showed hepatomegaly in all TPN groups compared with enteral formula feeding, consistent with our previous reports ( 4,26 ). Livers from all TPN pigs showed evidence of histopathological injury, including biliary duct dilation, portal tract cellular infi ltration, and microvascular steatosis.…”

Section: Discussionsupporting

confidence: 90%

“…However, the histological scores suggested that the features biliary injury and infl ammation were highest among the IL versus other lipid emulsion groups. Mouse models of cholestasis have shown blunted histological hepatotoxicity with fi sh oil ( 26,27 ). Collectively, these results suggest that fi sh oil-containing emulsions prevent the development of PNALD in TPN-fed neonatal pigs.…”

Section: Discussionmentioning

confidence: 72%

“…SL is a blend of lipids including soybean oil, MCTs, olive oil, and fi sh oil and thus contains phytosterols. The attention on phytosterols stems from their structural similarity with bile acids and earlier reports of phytosterolemia associated with PNALD in TPN-fed pediatric patients ( 4,26,28 ). After 2 weeks, the differences in phytosterol intake among the groups were directly refl ected in both the plasma and liver phytosterol concentrations, with the highest and lowest phytosterol levels in IL and OV pigs, respectively.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs

Vlaardingerbroek

Stoll

et al. 2014

Journal of Lipid Research

116

View full text Add to dashboard Cite

Cholestatic liver disease is one of the most common metabolic problems associated with total parenteral nutrition (TPN) in preterm infants, and it is strongly related to the duration of TPN ( 1 ). The incidence of parenteral nutrition-associated liver disease (PNALD) in infants who Abstract Total parenteral nutrition (TPN) is associated with the development of parenteral nutrition-associated liver disease (PNALD) in infants. Fish oil-based lipid emulsions can reverse PNALD, yet it is unknown if they can prevent PNALD. We studied preterm pigs administered TPN for 14 days with either 100% soybean oil (IL), 100% fi sh oil (OV), or a mixture of soybean oil, medium chain triglycerides (MCTs), olive oil, and fi sh oil (SL); a group was fed formula enterally (ENT). In TPN-fed pigs, serum direct bilirubin, gamma glutamyl transferase (GGT), and plasma bile acids increased after the 14 day treatment but were highest in IL pigs. All TPN pigs had suppressed hepatic expression of farnesoid X receptor (FXR), cholesterol 7-hydroxylase (CYP7A1), and plasma 7 ␣ -hydroxy-4-cholesten-3-one (C4) concentrations, yet hepatic CYP7A1 protein abundance was increased only in the IL versus ENT group. Organic solute transporter alpha (OST ␣ ) gene expression was the highest in the IL group and paralleled plasma bile acid levels. In cultured hepatocytes, bile acid-induced bile salt export pump (BSEP) expression was inhibited by phytosterol treatment. We show that TPN-fed pigs given soybean oil developed cholestasis and steatosis that was prevented with both This work was supported in part by federal funds from the USDA,, the American Society for Parenteral and Enteral Nutrition, Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BSEP, bile salt export pump; CA, cholic acid; CDCA, chenodeoxycholic acid; C4, 7 ␣ -hydroxy-4-cholesten-3-one; CYP8B1, sterol 12-alpha-hydroxylase; CYP7A1, cholesterol 7-hydroxylase; CYP3A29, cytochrome P450 3A29; CYP27A1, sterol 27-hydroxylase; FGF, fi broblast growth factor; FXR, farnesoid X receptor; GGT, gamma glutamyl transferase; MCT, medium chain triglyceride; MRP3, multidrug resistant protein 3; NTCP, Na + / taurocholate cotransporter; OBCA, obeticholic acid; OST ␣ / ␤ , organic solute transporters alpha and beta; PNALD, parenteral nutrition-associated liver disease; TPN, total parenteral nutrition; UDCA, ursodeoxycholic acid . and immediately placed in cages housed at 31°C to 32°C, as described previously ( 12 ). Based on body weight, pigs delivered from each sow were randomly assigned to one of the three TPN treatment groups or to enteral nutrition (ENT). After delivery, pigs were surgically implanted with catheters into the jugular vein and umbilical artery. Pigs in the enteral group also were implanted with an orogastric feeding tube, whereas TPN groups received a sham puncture. Maternal plasma (16 ml/kg intravenously during the fi rst 24 h) was administered for passive immunological protection. During the 14 day study, pigs received antibiotics (enrofl oxacin 5 mg/kg) intrave...

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs

Vlaardingerbroek

Stoll

et al. 2014

Journal of Lipid Research

116

View full text Add to dashboard Cite

show abstract

“…Thus, we hypothesized that saturated fatty acids augment TRB3 expression under conditions of ER stress and lead to apoptosis in human liver cells. It has previously been shown that the effect of TRB3 on survival or apoptosis are dependent on the cell type and context [18,23,30,31,32,33,34]. Here, we have demonstrated for the first time that TRB3 is significantly increased at the protein and mRNA level during palmitate-induced ER stress in the normal human liver cell line, L02, and that this higher expression level is associated with increased apoptosis.…”

Section: Discussionsupporting

confidence: 49%

Palmitate Induces TRB3 Expression and Promotes Apoptosis in Human Liver Cells

Yan

Wang

Xiao

et al. 2014

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Parenteral nutrition-associated liver disease (PNALD) is a major complication for patients who require long-term parenteral nutrition. Treatment options for PNALD are limited and its pathogenesis is poorly understood. Tribbles homolog 3 (TRB3) is a pseudokinase that modulates many signal transduction cascades and may be involved in the pathogenesis of PNALD. The aim of this study was to examine the role of TRB3 in palmitate-induced endoplasmic reticulum (ER) stress, in the human liver cell line L02. Methods: L02 cells were treated with palmitate, and its effect on cell viability, mitochondrial membrane potential, apoptosis and TRB3 expression were assessed. The role of TRB3 was also studied using transient overexpression of TRB3 in L02 cells, as well as its interaction with Akt signaling. Results: We found that palmitate induced ER stress and apoptosis in L02 cells. Palmitate-associated ER stress was accompanied by a significant induction of TRB3 expression at the mRNA and protein level. Overexpression of TRB3 potentiated the deleterious effects of palmitate, which was associated with decreased levels of phospho-Akt. Conclusions: TRB3 is an important mediator of palmitate-induced apoptosis in human liver cells, suggesting that it may also be involved in the molecular mechanism underlying PNALD.

show abstract

“…La solución de lípidos procedente de soja (Intralipid ® ) fue sustituida en las unidades pediátricas europeas por otras soluciones basándose en el desequilibrio en AGE por exceso de omega-6 y en la hepatotoxicidad (29) debida a la peroxidación lipídica y al efecto de los fitosteroles (30,31). Las soluciones mixtas de LCT y MCT (Lipofundina MCT/LCT 20% ® ) han sido administradas durante tiempo siendo bien toleradas incluso en lactantes pequeños (1).…”

Section: Requerimientos De Lípidosunclassified

Requerimientos en nutrición parenteral pediátrica

Costa¹,

Giner

2017

Nutr Hosp

View full text Add to dashboard Cite

INTRODUCCIÓNLa nutrición parenteral (NP) en el niño enfermo tiene como principal objetivo suministrar las demandas específicas de energía y nutrientes debidas a su enfermedad, manteniendo un balance de energía positivo que permita un crecimiento y desarrollo adecuados, procurando evitar tanto la infra como la sobrenutrición. REQUERIMIENTOS ENERGÉTICOSClásicamente, la principal preocupación a la hora de prescribir una NP era el no alcanzar las necesidades energéticas del paciente; sin embargo, actualmente, el problema se centra más en las consecuencias negativas a las que conduce el exceso o desequilibrio de los diversos nutrientes. La estimación de las necesidades energéticas en los niños con NP precisa considerar los distintos componentes del gasto energético y el hecho de que la mayoría de ellos están hospitalizados, inactivos, con o sin alimentación enteral concomitante y con diversos grados de estrés metabólico (1,2). COMPONENTES DEL GASTO ENERGÉTICO DEL NIÑOLa energía ingresada diariamente con los macronutrientes en su mayor proporción va a ser utilizada por el organismo (energía metabolizable), excepto una pequeña parte que se pierde de forma obligada (orina, heces, sudor). Esta energía disponible se va a consumir en el metabolismo basal, en la termogénesis de los alimentos (ambos constituyen el gasto energético en reposo, GER), en la termorregulación, en la actividad física y en el crecimiento (3). Este último es el que diferencia esencialmente la nutrición del niño respecto a la del adulto haciéndolo especialmente vulnerable en épocas de crecimiento acelerado sobre todo en el recién nacido pretérmino (RNPT) (1). La suma de todos ellos constituye el gasto energético total (GET) cuyo principal componente es el metabolismo basal (3). De este modo, el balance energético del niño será:Si sobra energía esta se almacenará en forma de grasa y si falta se movilizarán los depósitos orgánicos.En el niño enfermo estas circunstancias pueden variar considerablemente. Aunque hay que contemplar los requerimientos suplementarios para la recuperación de la desnutrición, se debe poner especial cuidado en evitar el exceso de energía debido a las complicaciones que puede comportar: esteatosis hepática, hiperglucemia e infecciones. Clásicamente se ha hecho un gran énfasis en el balance negativo generado por el estrés, sin embargo, diferentes estudios en niños sometidos a cirugía o que precisan cuidados intensivos demuestran que el aumento del gasto metabólico no es tan grande como se creía y se produce solo en las primeras 24 horas. En general, el paciente encamado tiene un GET generalmente disminuido por la inactividad lo que puede en parte compensar el incremento condicionado por diversos mecanismos (inflamación, pérdidas por ostomías...) (1,4,5). CÁLCULO DE LOS APORTES ENERGÉTICOS EN EL NIÑO CON NPEl cálculo de los requerimientos energéticos debe realizarse de forma individualizada, según edad, estado nutricional y enfermedad subyacente. En pacientes con enfermedades que conlleven alto riesgo de desnutrición (cirugía mayor...

show abstract

Effects of Long‐term Parenteral Nutrition on Serum Lipids, Plant Sterols, Cholesterol Metabolism, and Liver Histology in Pediatric Intestinal Failure

Abstract: Serum PS moderately increase during olive oil-based PN, and correlate positively with PN% and glutamyl transferase. Despite well-preserved liver function, histology often revealed significant liver damage.

Cited by 58 publications

References 44 publications

New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs

New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs

Palmitate Induces TRB3 Expression and Promotes Apoptosis in Human Liver Cells

Requerimientos en nutrición parenteral pediátrica

Contact Info

Product

Resources

About