Effects of glucose or fat calories in total parenteral nutrition on fat metabolism and systemic inflammation in rats

This study compared the effects of total parenteral nutrition (TPN) by central vein with or without fat provided at maintenance energy requirement on fatty acid metabolism, de novo lipogenesis, and the risk of hepatic and systemic inflammation in rats. Study I was conducted in 2 groups: high glucose (FIG), where fat-free TPN was given at maintenance levels of 180 kcal/(kg d), and low glucose (LG), where fat-free TPN containing 30% fewer calories at 126 kcal/(kg d) was provided by reducing 54 kcal/(kg d) from parenteral glucose. Study 2 contained 3 TPN groups: 1 LG group at 126 kcal/(kg d) and 2 groups at 180 kcal/(kg d) with 30% of total calories (54 kcal/[kg d]) either from soybean or fish oil emulsion. In both studies, animals fed a chow diet ad libitum were included. Plasma and hepatic triglyceride and phospholipid fatty acid profiles, enzymes indicating hepatic injury, and C-reactive protein levels (CRP) reflecting systemic injury were measured. In study 1, evidence of de novo lipogenesis was noted in LG and was more prominent in FIG with elevation of CRP in FIG. In study 2, de novo lipogenesis was reduced by adding either fat to LG to achieve maintenance energy levels. Moreover, adding fat as soybean oil but not fish oil significantly increased plasma and hepatic triglyceride and also elevated aspartate aminotransferase and CRP levels, reflecting inflammation. Thus, in rats, either hypocaloric feeding as glucose-based TPN or TPN provided at maintenance energy levels with the addition of fish oil limits hepatic lipid accumulation and prevents the evidence of hepatic and systemic injury found with maintenance level TPN as glucose only or glucose plus soybean oil. (C) 2011 Elsevier Inc. All rights reserved.Not LUMC related researc

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

Steatosis is a prominent feature of nonalcoholic fatty liver disease and a potential promoter of inflammation. Injury leading to cirrhosis is partly mediated by dysregulation of matrix protein turnover. Matrix metalloproteinase (MMP) inhibitors protect mice from lethal TNF-α induced liver injury. We hypothesized that Marimastat, a broad-spectrum MMP and TNF-α converting enzyme (TACE) inhibitor, might modulate this injury through interruption of inflammatory pathways. Triglyceride and phospholipid levels (liver, serum) and fatty acid profiles were used to assess essential fatty acid status and de novo lipogenesis as mechanisms for hepatic steatosis. Mice receiving a fat-free, high-carbohydrate diet (HCD) for 19 days developed severe fatty liver infiltration, demonstrated by histology, magnetic resonance spectroscopy, and elevated liver function tests. Animals receiving HCD plus Marimastat (HCD+MAR) were comparable to control animals. Increased tissue levels of peroxisome proliferator activated receptor-α (PPAR-α), higher levels of serum IL-6, and decreased levels of serum TNF-α receptor II were also seen in the HCD+MAR group compared with HCD-only. In addition, there was increased phosphorylation, and likely activation, of PPAR-α in the HCD+MAR group. PPAR-α is a transcription factor involved in β-oxidation of fatty acids, and IL-6 is a hepatoprotective cytokine. Liver triglyceride levels were higher and serum triglyceride and phospholipid levels lower with HCD-only but improved with Marimastat treatment. HCD-only and HCD+MAR groups were essential fatty acid deficient and had elevated rates of de novo lipogenesis. We therefore conclude that Marimastat reduces liver triglyceride accumulation by increasing fat oxidation and/or liver clearance of triglycerides. This may be related to increased expression and activation of PPAR-α or IL-6, respectively. Copyrigh