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Summary Background & aims Acute lung injury (ALI) is less severe in obese than in nonobese patients, but the mechanism is unclear. Secretory leukocyte protease inhibitor (SLPI) is the key anti-inflammatory protein in various lung diseases. We have previously reported changes of the surgical stress in obese rats using lard-based high-fat diet (HFD). The purpose of this study was to elucidate the effect of lard-based HFD on the pathophysiology of lipopolysaccharide (LPS)-induced ALI, and the role of SLPI expression. Methods Male Wistar rats were fed lard-based HFD (60 kcal% fat) or control diet (CD) for either 4 or 12 weeks and were killed after intraperitoneal LPS injection. Analyses included messenger RNA expression of TNF-α, macrophage inflammatory protein (MIP)-2, inducible nitric oxide synthase (iNOS), IL-10 and SLPI in the lung tissue and bronchoalveolar lavage fluid, and histology of the lungs. Results Rats fed HFD for 12 weeks showed suppression of the lung injury and oxidative stress after LPS injection, as indicated by reduction of pulmonary TNF-α, MIP-2 and iNOS mRNA expression and 8-hydroxy-2′-deoxyguanosine immunostaining. The increased pulmonary SLPI caused by lard was associated with decreased pro-inflammatory cytokines and oxidative stress, which eventually resulted in the prevention of ALI. Those effects of lard on LPS-induced ALI were greater after 12 weeks than after 4 weeks feeding, as indicated by the reduction of TNF-α, MIP-2 and iNOS levels. Conclusions Feeding lard-based HFD for 12 weeks attenuated LPS-induced ALI with increased pulmonary SLPI expression in rats.

Changes in the microbiota composition are able to affect nutrient absorption and energy metabolism, but there are few human studies. The aims were to analyze fecal constituents quantitatively and compare them with liver dysfunction in hepatic cancer patients and to evaluate the relationships among intestinal microbiota, fecal organic acids and plasma lipid composition.Fecal samples collected from 46 hepatic cancer patients (with liver cirrhosis, chronic hepatitis or liver fibrosis and normal liver) were evaluated for fecal constituents. Blood organic acid, lipid and fatty acid concentrations were analyzed.Fecal microbiota and organic acids showed no significant differences among different liver dysfunction patients. In normal liver patients, fecal Candida was positively correlated with plasma phospholipid while Bifidobacterium was negatively correlated with plasma eicosapentaenoic acid and eicosapentaenoic acid/arachidonic acid ratio (all p 0.05). In cirrhotic liver patients, positive correlations were noted for Lactobacillus and docosahexaenoic acid and Candida and eicosapentaenoic acid or eicosapentaenoic acid/arachidonic acid ratio (all p 0.01). It was suggested that intestinal biota affected serum fatty acid metabolism and were modified by liver disorders.Intestinal microbiota and organic acid concentrations in hepatic cancer patients had positive and/or negative correlations with serum lipid levels.

Summary Background & aims Short-chain fatty acids, especially butyrate, have various biological activities including inhibition of tumor necrosis factor (TNF)-α secretion, via attenuation of nuclear factor-κB (NF-κB) activation. Here, we evaluated the protective effect of oral administration of tributyrin, a prodrug of butyrate, on lipopolysaccharide (LPS)-induced liver injury in rats. Methods Rats were divided into four groups: normal control, tributyrin, LPS, and tributyrin/LPS (treated with tributyrin 1 h before LPS). Plasma levels of butyrate and TNF-α, expression of TNF-α, NF-κB, Toll-like receptor (TLR) 2, and TLR4 mRNA in liver, blood biochemical tests, and histopathological analysis of liver were performed. Results Oral tributyrin increased plasma butyrate level in the portal vein to 2.4 mM at 1 h and 0.7 mM at 2.5 h. Tributyrin attenuated NF-κB activation and liver tissue injury associated with LPS injection. The increases in TNF-α level, and hepatic TLR2 mRNA expression were lower in the tributyrin/LPS group. We believe that this study provides the first evidence that orally administered tributyrin increases butyrate level in the hepato-portal system and attenuates liver injury and subsequent inflammatory responses. Conclusion Oral tributyrin increased plasma butyrate in the portal vein and attenuated liver injury in endotoxemic rats.