The route of lipid administration affects parenteral nutrition–induced hepatic steatosis in a mouse model

Javid, Patrick J.; Greene, Arin K.; Garza, J. L. de la; Gura, Kathleen M.; Alwayn, Ian P. J.; Voss, Stephen G.; Nosé, Vânia; Satchi‐Fainaro, Ronit; Zausche, Blanca; Mulkern, Robert V.; Jaksic, Tom; Bistrian, Bruce R.; Folkman, Judah; Puder, Mark

doi:10.1016/j.jpedsurg.2005.05.045

Cited by 59 publications

(60 citation statements)

References 33 publications

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“…Broad-spectrum synthetic MMP inhibitors are also hepatoprotective in liver ischemia perfusion injury without a clear mechanism (14). We have developed an animal model (2,3,31) that utilizes a highcarbohydrate, no-fat diet that produces essential fatty acid deficiency. These animals develop steatosis and liver enzyme abnormalities in 19 days.…”

Section: Discussionmentioning

confidence: 99%

“…One section of liver was snap frozen and stored at Ϫ80°C for evaluation by magnetic resonance (MR) spectroscopy to determine the percentage liver fat content (2,31). MR imaging and spectroscopy were performed on a Bruker 8.5-T magnet.…”

Section: Methodsmentioning

confidence: 99%

“…Fatty acid analysis was conducted as described previously (1,2,31). Briefly, lipids were extracted from serum and livers and then fractionated into triglycerides and phospholipids by solid-phase chromatography using an aminopropyl column.…”

Section: Methodsmentioning

confidence: 99%

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Inhibition of matrix metalloproteinases increases PPAR-α and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model

Alwayn

Andersson

Lee³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Inhibition of matrix metalloproteinases increases PPAR-α and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model

Alwayn

Andersson

Lee³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…However, evidence accumulated over the past few decades strongly suggests the lipid component of TPN as the most probable cause of PNALD. Both animal and human research during the past decade has implicated phytosterols and v-6 (n-6) fatty acids as the most likely components in the current lipid formulations as primary reasons for PNALD (8)(9)(10)(11)(12). In contrast, fish oil-based lipid emulsions (FOLEs) have been shown to be associated with full resolution of PNALD (13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Fish Oil–Based Lipid Emulsions in the Treatment of Parenteral Nutrition-Associated Liver Disease: An Ongoing Positive Experience

Premkumar

Carter

Hawthorne

et al. 2014

Advances in Nutrition

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We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutritionassociated liver disease (PNALD). In this report, we share our ongoing experience at Texas Children's Hospital, Houston, Texas in the use of FOLE in treatment of PNALD as presented at the 2013 Experimental Biology meeting. We describe the findings of a single center, prospective, observational study of infants <6 mo of age with PNALD who received parenteral FOLE as monotherapy. A total of 97 infants received FOLE under the compassionate-use protocol for the treatment of PNALD. Eighty-three (86%) survived with resolution of cholestasis and 14 (14%) died. The median conjugated bilirubin (CB) concentration at the initiation of FOLE therapy was 4.8 mg/dL (range 2.1-26). The median time to resolution of cholestasis was 40 d (range 3-158). Compared with infants with mild cholestasis (CB of 2.1-5 mg/dL at the initiation of FOLE), nonsurvivors were significantly more premature and took longer to resolve their cholestasis. Gestational age at birth correlated inversely with CB at the beginning of FOLE and peak CB. Infants with an initial CB >10 mg/dL had a higher mortality rate than infants with an initial CB <5 mg/dL (35% vs. 6%; P < 0.05). Our experience with the use of FOLE in PNALD continues to be encouraging. Prematurity continues to be a major determinant in mortality and severity of cholestasis. This calls for further controlled studies designed to optimize dose and timing of intervention in the use of FOLE in neonates. Adv. Nutr. 5: 65-70, 2014.

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“…Intravenous lipids are a critical component of PN solutions by providing essential fatty acids and dense calories. However, fat emulsions have also been implicated as a significant cause of PNALD [11,12]. The precise mechanisms by which fat emulsions contribute to PNALD are not well understood, although there are likely multiple mechanisms at work.…”

Section: Pathophysiology Of Liver Disease In Sbsmentioning

confidence: 99%

The rationale for the use of parenteral omega-3 lipids in children with short bowel syndrome and liver disease

et al. 2008

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Parenteral nutrition associated liver disease (PNALD) is the major source of morbidity and mortality in children with short bowel syndrome (SBS). There is emerging evidence that omega-6 fatty acids (omega6FA) within the parenteral solution play a major role in PNALD and their effects may be reversed or ameliorated by substitution with omega-3 fatty acids (omega3FA). This paper reviews the mechanisms whereby omega3FAs may influence PNALD by improving bile flow, inhibiting steatosis, and having immunomodulatory effects. The early clinical experience with omega3FAs in SBS and PNALD is briefly reviewed and the implications of such, and future directions are considered.

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The route of lipid administration affects parenteral nutrition–induced hepatic steatosis in a mouse model

Cited by 59 publications

References 33 publications

Inhibition of matrix metalloproteinases increases PPAR-α and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model

Inhibition of matrix metalloproteinases increases PPAR-α and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model

Fish Oil–Based Lipid Emulsions in the Treatment of Parenteral Nutrition-Associated Liver Disease: An Ongoing Positive Experience

The rationale for the use of parenteral omega-3 lipids in children with short bowel syndrome and liver disease

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