Soybean Oil Fat Emulsion to Prevent TPN-Induced Liver Damage: Possible Molecular Mechanisms and Clinical Implications

Abstract

INTRODUCTIONTotal parenteral nutrition (TPN), which is recognized as one method for parenteral hyperalimentation, has been found to be an effective and relatively safe method for supplying energy and nutrients to surgical patients. Following improvements in parenteral regimens including vitamins and trace elements and in catheter techniques to reduce the septic complications associated with TPN, TPN has been widely employed to provide complete nutritional support and therapeutic benefits in a variety of pathophysiological settings in which patients are unable to eat. However, TPN-induced hepatobiliary dysfunction, which was first described by Peden et al.,1) has been recognized as a cause of severe morbidity and a life-threatening complication of TPN, especially in neonates and infants. Hepatic dysfunction with steatosis is the most common complication associated with fat-free TPN in adults, and cholestasis is more common in infants.2,3) Recently, the 3-component infusion solution containing amino acids, glucose, and soybean oil emulsion, GA-1080 (MIXID ® , Otsuka Pharmaceutical Factory, Inc.; Tokushima, Japan), has been demonstrated to be effective in overcoming such hepatic morbidity in clinical studies.4) Intravenous fat emulsions, especially soybean oil, are now available as a source of essential fatty acids in patients receiving TPN, and the "three-in-one" solution GA-1080 has been found to be clinically safe, stable, and economical. However, the multifactorial pathogenesis of TPN-induced hepatic dysfunction remains unclear, and the molecular mechanisms by which GA-1080 prevents hepatic dysfunction have not yet been identified.We have recently developed an infant rat model of hepatobiliary dysfunction.5) Using this animal model, we have clearly demonstrated the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN in infant rats. Furthermore, we have shown that including fat in the TPN regimen is very important in preventing TPN-induced hepatic dysfunction. In this review, we describe the molecular mechanisms and the clinical implications of soybean oil in TPN solutions in avoiding the hepatic complications associated with parenteral nutrition. INFANT RAT TPN MODEL WITH HEPATOBILIARY DYSFUNCTIONSince the first studies of TPN in animal models conducted in 1968 by Dudrick et al.,6) it has been known that only a limited number of species (such as the dog, cat, rabbit, and guinea pig) can tolerate the surgical procedures required for TPN, and few studies have employed rats as an animal model for TPN. In 1981, Tashiro and Meng 7) were the first to report a technique for long-term TPN in unrestrained weanling or infant (3-week-old) rats, thus establishing an animal model for pediatric TPN. Numerous studies have focused on the optimal TPN composition in mature rats, but few have addressed this issue in infant rats.We have recently developed an infant rat model with hepatic dysfunction and steatosis induced by overdose of fatfree TPN. 5) After 30 infant (3-week-ol...

Soybean fat supplementation controls insulin resistance caused by fat-free total parenteral nutrition

“…However, forced administration of high glucose, as in fat-free TPN, caused fatty liver, as previously reported by Oshita et al (2004). Further, Nishimura et al (2006) recently reported that high serum glucose during the administration of fat-free TPN in infant rats decreased gluconeogenesis-and lipolysis-related gene expression in the liver but increased the expression of acetylcoenzyme A carboxylase (ACC), a key enzyme in lipogenesis, resulting in the accumulation of lipids in the liver. On the other hand, despite the fatty liver, serum lipid concentrations were significantly lower in the fat-free TPN group.…”

Bile acid transporters and regulatory nuclear receptors in the liver and beyond

“…In addition, stigmasterol, a soy-derived lipid, antagonizes FXR activity [47]. Interestingly, the addition of soybean fat emulsion prevents hepatic injury by TPN possibly by stimulating PPARα [48]. Notably, intensive insulin therapy reduces cholestasis and biliary sludge in critically ill patients [49], which may be linked to regulation of FXR expression by glucose [50].…”

Short-Term Intravenous Fish-Oil Emulsions in Pediatric Oncologic Patients—Effect on Liver Parameters

“…The study of Gura et al provides data, which allow the interpretation that PNLD potentially can be reversed when continuing parenteral soybean-based lipid solutions. Furthermore, animal studies have shown reversal of cholestasis using soybean oil (6,24). However, our observation of increased γ GT levels in the group receiving soybean-based lipids, and the growing evidence of clinical trials showing reversal of cholastasis (bilirubin and γ GT) support the conclusion of the beneficial effects of fish oil or fish oil-containing lipid solutions on PNLD.…”