A cafeteria diet triggers intestinal inflammation and oxidative stress in obese rats.

The gastrointestinal alterations associated with the consumption of an obesogenic diet, such as inflammation, permeability impairment and oxidative stress, have been poorly explored in both diet-induced obesity (DIO) and genetic obesity. The aim of the present study was to examine the impact of an obesogenic diet on the gut health status of DIO rats in comparison with the Zucker (fa/fa) rat leptin receptor-deficient model of genetic obesity over time. For this purpose, female Wistar rats (n 48) were administered a standard or a cafeteria diet (CAF diet) for 12, 14·5 or 17 weeks and were compared with fa/fa Zucker rats fed a standard diet for 10 weeks. Morphometric variables, plasma biochemical parameters, myeloperoxidase (MPO) activity and reactive oxygen species (ROS) levels in the ileum were assessed, as well as the expressions of proinflammatory genes (TNF-α and inducible nitric oxide synthase (iNOS)) and intestinal permeability genes (zonula occludens-1, claudin-1 and occludin). Both the nutritional model and the genetic obesity model showed increased body weight and metabolic alterations at the final time point. An increase in intestinal ROS production and MPO activity was observed in the gastrointestinal tracts of rats fed a CAF diet but not in the genetic obesity model. TNF-α was overexpressed in the ileum of both CAF diet and fa/fa groups, and ileal inflammation was associated with the degree of obesity and metabolic alterations. Interestingly, the 17-week CAF group and the fa/fa rats exhibited alterations in the expressions of permeability genes. Relevantly, in the hyperlipidic refined sugar diet model of obesity, the responses to chronic energy overload led to time-dependent increases in gut inflammation and oxidative stress.

Liver lipocalin 2 expression in severely obese women with non alcoholic fatty liver disease.

BACKGROUND: Lipocalin 2 (LCN2) has been related to obesity, insulin resistance and metabolic disturbance. However, its relation with non alcoholic fatty liver disease (NAFLD) has hardly been studied. METHODS: We examined LCN2 circulating levels and its protein and gene expression in liver from women with severe obesity and NAFLD. We analyzed the liver histology of 59 white severely obese women (BMI ≥40 Kg/m²): 15 subjects presented normal liver histology or non-significant liver disease (NL), 18 simple steatosis (SS) and 26 non alcoholic steatohepatitis (NASH). We determined the anthropometric and metabolic features of the women. LCN2 levels were determined by an ELISA and liver mRNA expression by real time RT-PCR. We also studied LCN2 expression in HepG2 liver cells under various inflammatory stimuli. RESULTS: Liver LCN2 protein and gene expression were higher in NAFLD than in obese with NL. Liver LCN2 gene expression correlated with SS (r=0.351, p=0.016), and its protein expression correlated with NASH (r=0.705, p=0.003). LCN2 expression was detected in HepG2 cells after the administration of TNFα, IL6, resistin or adiponectin. LCN2 expression was induced by TNFα, IL6 and resistin. CONCLUSIONS: Liver LCN2 is related to NAFLD in severely obese women. Up-regulation of LCN2 expression is detected in HepG2 cells after exposure to TNFα, IL6 and resistin. These results suggest that LCN2 expression is induced under liver harmful conditions.

Procyanidin dimer B1 and trimer C1 impair inflammatory response signalling in human monocytes.

The way specific procyanidins exert their anti-inflammatory effects is not fully understood. This study has investigated the capacity of different procyanidins to modulate lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production in THP1 human monocytes and their effects on the redox regulated protein kinases activity: IkB kinase beta (IKKb) and the extracellular signal-regulated kinase (ERK). LPS-triggered increase of ROS was prevented by cell pre-incubation with procyanidins. LPS induced ERK1/2 activation through phosphorylation, which was inhibited by all the compounds tested, the most active being epigallocatechin (EG), followed by epigallocatechin gallate (EGCG) and C1. Procyanidins inhibited IKKb activity in vitro. C1 and procyanidin extract (PE) exerted the maximal IKKb inhibition, followed by EGCG and dimer B1. Catechin exerted a slight but significant IKKb inhibition, in contrast to epicatechin, which was ineffective. In conclusion, procyanidins reduce the LPS-induced production of ROS and they exert their anti-inflammatory effects by inhibiting ERK1/2 and IKKb activity.