Endotoxemia and hepatic injury in a rodent model of hindlimb unloading

Rivera, Chantal A.; Tcharmtchi, M. Hossein; Mendoza, Leobardo; Smith, Carine

doi:10.1152/japplphysiol.00302.2003

Cited by 36 publications

(40 citation statements)

References 47 publications

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“…Our previous work and the present study (Fig. 3) demonstrated that lipid droplets accumulated in the cytoplasm of hepatocytes (38). Vecchini et al (46) investigated mechanisms underlying hepatic steatosis resulting from HU and found that mRNA levels and activities of several proteins that modulate hepatic lipid content were altered in favor of lipid accumulation.…”

Section: Discussionsupporting

confidence: 65%

“…However, under pathophysiological conditions, intestinal permeability can increase significantly, allowing bacteria and bacterial components to leak into the circulation. In a previous study, we demonstrated that lowgrade portal endotoxemia was associated with hepatic injury in rats and C57BL/6 mice after HU (38). In contrast, no histological changes or significant increases in serum ALT activity were detected after HU in endotoxin-resistant C3H/HEJ mice despite portal endotoxin levels of 222 Ϯ 83.4 pg/ml.…”

Section: Mechanism Of Injury Involves Endotoxemia and Lipid Peroxidatmentioning

confidence: 84%

“…Using the HU model, we recently reported hepatic injury and inflammation in endotoxin-sensitive rodents, as indicated by increased neutrophil content and elevated serum transaminase activity (38). Cytoplasmic accumulation of fat in hepatocytes was also observed, a phenomenon most likely resulting from altered lipogenesis.…”

mentioning

confidence: 97%

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Feeding a corn oil/sucrose-enriched diet enhances steatohepatitis in sedentary rats

Rivera¹,

Abrams²,

Tcharmtchi³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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The current study investigated the combined effects of feeding a high-fat/high-sucrose (HF/HS) diet to rodents rendered sedentary via hindlimb unloading (HU). For 3 wk before HU, male Wistar rats were fed chow or a diet in which 32% of calories were derived from corn oil fat and 48% of calories from sucrose. Feeding continued during an additional 3-wk period of HU. Subsequently, blood samples were collected for determination of circulating leukocyte counts, insulin levels, and portal vein endotoxin. Inflammation, necrosis, and steatosis were assessed in formalin-fixed liver sections. No biochemical or histological evidence of injury was observed in control rats fed chow or HF/HS. HU increased circulating neutrophils and resulted in hyperinsulinemia. Mild hepatic fat accumulation and minimal focal necroinflammation were observed in this group. Feeding HF/HS during HU exacerbated hyperinsulinemia, hepatic steatosis, Kupffer cell content, and cytokine expression. Significant portal endotoxemia was noted in HU rats but was not influenced by HF/HS diet. On the other hand, feeding HF/HS significantly enhanced lipid peroxidation end products in liver of HU rats by approximately threefold compared with chow-fed rats. In summary, these findings demonstrate that feeding a high-calorie diet potentiates steatosis and injury in sedentary HU rats. Mechanisms underlying enhanced injury most likely involved lipid peroxidation. Importantly, these findings suggest that dietary manipulation combined with physical inactivity can be used to model steatohepatitis.

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Section: Discussionsupporting

confidence: 65%

Section: Mechanism Of Injury Involves Endotoxemia and Lipid Peroxidatmentioning

confidence: 84%

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Feeding a corn oil/sucrose-enriched diet enhances steatohepatitis in sedentary rats

Rivera¹,

Abrams²,

Tcharmtchi³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Evidently, the intestinal epithelium acts as a continuous barrier to avoid LPS translocation, but some endogenous or exogenous factors may alter this function. Among the factors promoting a leaky gut and increasing plasma LPS levels, alcohol consumption (29 -33), immobilization stress (33,34), and radiation (35) have been put forward. Most importantly, in most of these studies, antibiotic treatments were also administered and resulted in reduced plasma and cecal LPS levels.…”

Section: Discussionmentioning

confidence: 99%

Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice

et al. 2008

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OBJECTIVE-Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases. RESEARCH DESIGN AND METHODS-We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect.RESULTS-We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat-fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14 Ϫ/Ϫ mutant mice mimicked the metabolic and inflammatory effects of antibiotics.CONCLUSIONS-This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.

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“…Under simulated weightlessness, intestinal congestion and mucosa swelling were caused by dysfunction of mesentery minicirculation [16] , intestinal motivation was slowed down, colonic transit time was prolonged [17] and intestinal flora was altered [2] . All these abnormal changes may further cause inflammatory cytokines activation (such as IFN-r and TNF-α) [18] . It was reported the expression of TJ proteins could be regulated by IFN-γ or TNF-α [19,20] .…”

Section: Discussionmentioning

confidence: 99%

Effects of simulated weightlessness on tight junction protein occludin and Zonula Occluden-1 expression levels in the intestinal mucosa of rats

Chen

Yang

Liu

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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This study investigated the tight junction (TJ) protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness. Twenty-four Wistar rats were randomly divided into three groups: CON group (n=8), control; SUS-14 d group (n=8), tail-suspension for 14 days; SUS-21 d group (n=8), tail-suspension for 21 days. Occludin and Zonula Occluden-1 (ZO-1) expression levels were determined by immunohistochemical analysis and mRNA fluorescent quantitative PCR. Plasma levels of diamine oxidase (DAO) and d-lactate were determined using enzymatic spectrophotometry. Immunohistochemical results for occludin and ZO-1 showed disruption of the TJs in the intestinal mucosa in SUS-14 d and SUS-21 d groups. The expression levels of occludin and ZO-1 in SUS-21 d group were lower than those in SUS-14 d group, and significantly lower than those in CON group (Occldin: 0.86±0.02 vs 1.01±0.03 vs 1.63±0.03 and ZO-1: 0.82±0.01 vs 1.00±0.02 vs 1.55±0.01, P<0.01). Moreover, the levels of plasma DAO and d-lactate in SUS-21 d group were higher than those in SUS-14 d group, and significantly higher than those in CON group (DAO: 27.58±0.49 vs 20.74±0.49 vs 12.94±0.21 and d-lactate: 37.86±0.74 vs 28.26±1.01 vs 17.76±0.91, P<0.01). There were significant negative correlations between occludin or ZO-1 expression levels and DAO (r (2)=0.9014, r (2)=0.9355, P<0.01) or d-lactate levels (r (2)=0.8989, r (2)=0.9331, P<0.01). Occludin and Zo-1 were reduced in intestinal mucosa both in mRNA and protein levels in the rat tail-suspension model. The significant negative correlations between expression levels of TJs and plasma levels of DAO or d-lactate support the hypothesis that intestinal permeability is increased due to a decrease in TJ protein expression during tail-suspension from 14 days to 21 days.

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Endotoxemia and hepatic injury in a rodent model of hindlimb unloading

Cited by 36 publications

References 47 publications

Feeding a corn oil/sucrose-enriched diet enhances steatohepatitis in sedentary rats

Feeding a corn oil/sucrose-enriched diet enhances steatohepatitis in sedentary rats

Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice

Effects of simulated weightlessness on tight junction protein occludin and Zonula Occluden-1 expression levels in the intestinal mucosa of rats

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