Effects of lipid administration on liver apoptotic signals in a mouse model of total parenteral nutrition (TPN)

Abstract

Lipids are an important component of total parenteral nutrition (TPN), contributing the largest caloric load per volume of solution and providing essential fatty acids necessary for survival. However, lipids are known to be causative factors in oxidative stress, which are expressed via the Bcl-2 family of proteins and/or Fas-mediated apoptosis in several tissues. Interestingly, we have recently observed an increase in hepatocyte apoptosis with administration of TPN. To address the mechanism of this apoptosis, we investigated the effects of parenteral lipid administration on apoptotic signaling in a mouse model. C57BL/6J male mice received physiologic saline and standard chow (control) or standard TPN solution with (TPN+L) or without lipid (TPN-L) emulsion. After 7 days of infusion, apoptosis increased in the TPN+L at a significantly higher rate compared with control and TPN-L groups ( p<0.05). Both TPN, with and without lipids, suppressed the pro-apoptotic signals Bid and Bcl-xs ( p<0.05). In contrast, TPN with lipid increased the expression of Fas and both the pro-apoptotic factor Bad and the anti-apoptotic factor Bcl-xl ( p<0.05). These changes may contribute to TPN-induced hepatocyte injury (apoptosis) or suppress the ability of liver hepatocytes to regenerate.

Oxidative injury and hepatocyte apoptosis in total parenteral nutrition–associated liver dysfunction

“…By TUNEL staining, the PN-10 group exhibited significant increase in apoptosis index compared with other groups, as well as for the peroxidation marker-MDA content. The proportion of hepatocyte apoptosis was high (44.59 F 6.68) compared with the result of the Tazuke et al study (0.56 F 0.03) [11], which might be explained by the use of different animals at different times of life and different counting system as well. The difference between the PN-7 and PN-10 groups was obvious, which might infer an accumulative effect in the process of liver injury.…”

Mitochondria-initiated apoptosis triggered by oxidative injury play a role in total parenteral nutrition–associated liver dysfunction in infant rabbit model

“…An animal experiment demonstrated that TPN with lipid increased the expression of Fas and both the proapoptotic factor Bad and the antiapoptotic factor Bcl-xl. These changes may contribute to TPN-induced hepatocyte injury (apoptosis) or may suppress the ability of liver hepatocytes to regenerate [19].…”

Reduction of hepatocellular injury after common bile duct ligation using omega-3 fatty acids

“…Parenteral nutrition-associated liver disease is characterized by a spectrum of fatty liver disease, inflammation, bile duct proliferation, fibrosis, and cirrhosis. Biochemically, the disease is in part because of TNF-α-mediated inflammation and FasL-mediated apoptosis in animal models [15,16]. In our initial studies, we hypothesized that the development of PNALD may be dependent on the type of fat administered (soybean oil-based vs fish oil-based) and that omega-3 fatty acids would prevent or reduce de novo lipogenesis and subsequent liver injury.…”