Early macrophage response to obesity encompasses Interferon Regulatory Factor 5 regulated mitochondrial architecture remodelling.

Adipose tissue macrophages (ATM) adapt to changes in their energetic microenvironment. Caloric excess, in a range from transient to diet-induced obesity, could result in the transition of ATMs from highly oxidative and protective to highly inflammatory and metabolically deleterious. Here, we demonstrate that Interferon Regulatory Factor 5 (IRF5) is a key regulator of macrophage oxidative capacity in response to caloric excess. ATMs from mice with genetic-deficiency of Irf5 are characterised by increased oxidative respiration and mitochondrial membrane potential. Transient inhibition of IRF5 activity leads to a similar respiratory phenotype as genomic deletion, and is reversible by reconstitution of IRF5 expression. We find that the highly oxidative nature of Irf5-deficient macrophages results from transcriptional de-repression of the mitochondrial matrix component Growth Hormone Inducible Transmembrane Protein (GHITM) gene. The Irf5-deficiency-associated high oxygen consumption could be alleviated by experimental suppression of Ghitm expression. ATMs and monocytes from patients with obesity or with type-2 diabetes retain the reciprocal regulatory relationship between Irf5 and Ghitm. Thus, our study provides insights into the mechanism of how the inflammatory transcription factor IRF5 controls physiological adaptation to diet-induced obesity via regulating mitochondrial architecture in macrophages.

Soya bean tempe extracts show antibacterial activity against Bacillus cereus cells and spores.

AIMS: Tempe, a Rhizopus ssp.-fermented soya bean food product, was investigated for bacteriostatic and/or bactericidal effects against cells and spores of the food-borne pathogen Bacillus cereus. METHODS AND RESULTS: Tempe extract showed a high antibacterial activity against B. cereus ATCC 14579 based on optical density and viable count measurements. This growth inhibition was manifested by a 4 log CFU ml(-1) reduction, within the first 15 min of exposure. Tempe extracts also rapidly inactivated B. cereus spores upon germination. Viability and membrane permeability assessments using fluorescence probes showed rapid inactivation and permeabilization of the cytoplasmic membrane confirming the bactericidal mode of action. Cooked beans and Rhizopus grown on different media did not show antibacterial activity, indicating the unique association of the antibacterial activity with tempe. Subsequent characterization of the antibacterial activity revealed that heat treatment and protease addition nullified the bactericidal effect, indicating the proteinaceous nature of the bioactive compound. CONCLUSIONS: During fermentation of soya beans with Rhizopus, compounds are released with extensive antibacterial activity against B. cereus cells and spores. SIGNIFICANCE AND IMPACT OF STUDY: The results show the potential of producing natural antibacterial compounds that could be used as ingredients in food preservation and pathogen control.

Spontaneous baroreflex cardiac sensitivity in end-stage liver disease: effect of liver transplantation.

BACKGROUND AND OBJECTIVE: End-stage liver disease is associated with an imbalance in the autonomic nervous system. The purpose of this study was to estimate the effect of liver transplantation on this imbalance. METHOD: The study involved 10 patients undergoing liver transplantation and 9 patients without liver impairment undergoing liver surgery. The spontaneous baroreflex sensitivity was measured before and 1 month after surgery for the liver surgery group; before and 1, 3, 6, 12 and 18 months after orthotopic liver transplantation. RESULTS: The spontaneous baroreflex slope of patients with end-stage liver disease was decreased before liver transplantation compared to the liver surgery group (3.9 +/- 2.5 ms mmHg(-1) vs. 9.9 +/- 5.0 ms mmHg(-1), P = 0.002). The mean slope was significantly increased at 12 and 18 months compared to the pre-transplantation value (3.9 +/- 2.5 ms mmHg(-1) vs. 8.1 +/- 6.6 ms mmHg(-1) and 7.4 +/- 4.8 ms mmHg(-1), respectively; P = 0.042). Nevertheless, further analysis of individual data showed that only four patients exhibited a marked increase in their baroreflex slope 12 months after the liver transplantation whereas it remained decreased in the six others. CONCLUSIONS: These results confirm that the baroreflex sensitivity is depressed in end-stage liver disease in line with an autonomic nervous system imbalance. The liver transplantation reverses this disturbance only in some patients.

Time course of oxidative stress after major burns.

OBJECTIVE: To evaluate oxidative stress resulting from major burns in humans. DESIGN: Prospective clinical study with control group. SETTING: Mechanically ventilated adult patients admitted with more than 30% total burn surface area. PATIENTS AND PARTICIPANTS: 20 patients with a mean body surface burned area of 54%. MEASUREMENTS AND RESULTS: The oxidative stress evaluation was based on measurements of trace elements, vitamins, antioxidant enzymatic activity and end-products of lipid peroxidation. During the first 5 days after injury burn patients exhibit a decrease in selenium and antioxidant vitamins (C, beta-carotene, lycopene) and an increase in lipid peroxidation products (TBARS). CONCLUSION: Our results suggest that major burn is associated with oxidative stress during the 5 days after the initial injury, as demonstrated by a simultaneous decrease in antioxidant vitamins and a large increase in TBARS.