A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death.

In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is compromised by a quick decline in the expression of hepatic PPARα, a transcription factor essential in intracellular catabolism of free fatty acids. The mechanism upstream of this PPARα downregulation is unknown. We found that sepsis causes a progressive hepatic loss-of-function of HNF4α, which has a strong impact on the expression of several important nuclear receptors, including PPARα. HNF4α depletion in hepatocytes dramatically increases sepsis lethality, steatosis, and organ damage and prevents an adequate response to IL6, which is critical for liver regeneration and survival. An HNF4α agonist protects against sepsis at all levels, irrespectively of bacterial loads, suggesting HNF4α is crucial in tolerance to sepsis. In conclusion, hepatic HNF4α activity is decreased during sepsis, causing PPARα downregulation, metabolic problems, and a disturbed IL6-mediated acute phase response. The findings provide new insights and therapeutic options in sepsis.

Migration of surrogate contaminants from paperboard to foods: Effect of food and surrogate properties.

The current research describes an alternative test method to evaluate the impact of food properties and compound characteristics on migration from paperboard to food. Tightly sealed bottles containing paperboard spiked with surrogate components as a donor, together with modified polyphenylene oxide (MPPO or Tenax®) or one of the nine considered foods as a receptor, were stored at 22°C. Instead of analysing the receptor, migration from donor to receptor was followed up by evaluating the recovery of surrogates from the donor over time, thus avoiding challenges in the analysis of the foods as such. Free fat content affected the migration more than the specific surface area of the food, reaching a plateau at fat contents >8.1%. The highest migration was observed to fatty foods such as biscuits (8% to 25% fat) and chocolate (40% fat). Intermediate migration occurred to starchy and particulate foods such as egg-based wheat pasta (2.6% fat), wheat flour (1% fat) and rice flour (0.5% fat). Low migration occurred in the case of paperboard in contact with wheat pasta (0.4% fat). Native starch was found to be more sensitive to migration than gelatinised starch. Volatility was identified as the most important characteristic of the migrating compounds. MPPO was considered as a suitable surrogate for dry foods as it did not underestimate migration in any case. However, for low-fat foods such as wheat pasta, clear overestimations could occur, but only for volatile surrogates with vapour pressure over 1.45 mTorr.