Dietary fructans modulate polyamine concentration in the cecum of rats

Nondigestible but fermentable dietary fructans such as oligofructose exert many effects on gut physiology through their fermentation end products such as short-chain fatty acids. Could other metabolites be produced in the gut and contribute to the physiologic effects of dietary fructans? The aim of the study was to evaluate the influence of oligofructose on putrescine, spermidine and spermine concentrations in the cecum, the portal vein and the liver of rats and to assess their involvement in cecal enlargement and the modulation of hepatic lipid metabolism. Putrescine, spermidine and spermine were quantified by HPLC in samples obtained from male Wistar rats fed a nonpurified standard diet (controls) or the same diet enriched with 10 g/100 g oligofructose (OFS) for 4 wk. OFS-fed rats had significantly greater cecal content and tissue weights. OFS almost doubled the concentration of putrescine in the cecal contents. The concentration of all three polyamines in the cecal tissue was significantly greater than in controls. The concentration of spermidine in portal plasma was lower in rats fed OFS, whereas the treatment did not affect the polyamine concentrations in the liver. The fermentation of dietary fructans contributed to an increase in the concentration of putrescine in the gut without modifying putrescine concentration in either the portal blood or liver. Moreover, the greater levels of polyamines in cecal tissue may be related to the cell proliferation resulting from OFS fermentation in the gut.     

Dietary oligofructose lessens hepatic steatosis, but does not prevent hypertriglyceridemia in obese zucker rats

We studied the influence of oligofructose (OFS), a nondigestible fructan, on lipid metabolism in obese fa/fa Zucker rats. The addition of 10 g/100 g OFS to the diet slowed the increase in body weight without modifying serum triglycerides or glucose concentrations after 7 wk of treatment. However, an oral load of 2 g glucose and 5 g corn oil/kg body weight increased triglyceridemia more in OFS-fed rats than in control rats. After 10 wk, OFS decreased the hepatic concentration of triglycerides 57% relative to controls. The less severe steatosis was confirmed by histologic analysis. Among the key enzymes involved in fatty acid synthesis and esterification, only malic enzyme activity was significantly lower in OFS-fed rats than in controls. The epididymal fat mass was significantly lower in OFS-fed rats. In conclusion, dietary enrichment with OFS can counteract both the fat mass development and the hepatic steatosis that occur in obese Zucker rats. Future studies will be designed to clarify in obese animals the influence of dietary OFS on postprandial triglyceridemia, which is an important variable associated with the development of atherosclerosis in humans, and to analyze the biochemical mechanism underlying the "hepatoprotective" effect of OFS.     

Microbiome response to diet: focus on obesity and related diseases

Numerous studies in humans and animal models describe disturbances of the gut microbial ecosystem associated with adiposity and hallmarks of the metabolic syndrome, including hepatic and cardiovascular diseases. The manipulation of the microbiome, which is largely influenced by the diet, appears as an innovative therapeutic tool to prevent or control obesity and related diseases. This review describes the impact of nutrients on the gut microbiota composition and/or function and when available, the consequences on host physiology. A special emphasis is made on the contribution of bacterial-derived metabolites in the regulation of key gut functions that may explain their systemic effect.

     

Lipides et inflammation postprandiale : impact du microbiote intestinal

Obesity and type 2 diabetes are associated with low-grade inflammatory tone. Growing evidence demonstrates that the gut microbiota is involved not only in the host metabolism but also in the pathogenesis of the low grade inflammation associated with obesity and type 2 diabetes. Among the mechanisms, dietary habits and more specifically the nutritional composition of the diet (lipids, non-digestible carbohydrates) have been shown to participate to the modulation of the composition and the activity of the gut microbiota. These questions and mechanisms will be discussed following experimental data.     

Insulin increases the sensitivity of tumors to irradiation: involvement of an increase in tumor oxygenation mediated by a nitric oxide-dependent decrease of the tumor cells oxygen consumption

The effects of insulin on tumor oxygenation, perfusion, oxygen consumption,and radiation sensitivity were studied on two different mouse tumor models (TLT, a liver tumor, and FSAII, a fibrosarcoma). Anesthetized mice were infused with insulin i.v. at a rate of 16 milliUnits/kg/min for 25 min. Local tumor oxygenation measurements were carried out using two independent techniques: electron paramagnetic resonance oximetry and a fiber-optic device (OxyLite). Two complementary techniques were also used to assess the blood flow inside the tumor: a laser Doppler system (OxyFlo) and contrast-enhanced magnetic resonance imaging. The oxygen consumption rate of tumor cells after in vivo insulin infusion was measured using high frequency electron paramagnetic resonance oximetry. To know if insulin was able to enhance radiation-induced tumor regrowth delay, tumor-bearing mice were treated with 16 Gy of 250 kV radiation dose after insulin infusion. We provide evidence that insulin increases the local pressure of oxygen of tumors (from 0-3 mm Hg to 8-11 mm Hg) as well as the tumor response to irradiation (increasing regrowth delay by a factor of 2.11). We found that the insulin-induced increase of tumor pressure of oxygen: (a) is not caused by an increase in the tumor blood flow, which is even decreased after insulin infusion; (b) is because of a decrease in the tumor cell oxygen consumption (in vivo insulin consumed oxygen three times slower than control cells); and (c) is inhibited by a nitric oxide (NO) synthase inhibitor, Nomega-nitro-L-arginine methyl ester, when injected i.p. at 15 micromol/kg(-1), 1 h before insulin infusion. We demonstrate by immunoblotting that the NO pathway involves a phosphorylation of endothelial NO synthase and showed a concomitant increase in the cyclic GMP tumor level. These findings provide unique insights into biological processes in tumors, new possible management for treating cancer patients, and raise major questions about the role of insulin secretion (fasting status and diabetes) in the clinical response of tumors to radiation therapy.     

Kupffer cell activity is involved in the hepatoprotective effect of dietary oligofructose in rats with endotoxic shock

In the present study, we tested the hypothesis that dietary oligofructose (FOS) can modulate both the response to an endotoxic shock induced by lipopolysaccharide (LPS) administration and the activity of resident hepatic macrophages, i.e., Kupffer cells. Male Wistar rats (n = 5-9 per group) were fed a standard diet or a diet supplemented with 10 g/100 g FOS for 3 wk. LPS (10 mg/kg) or saline were injected i.p. after dietary treatment. After LPS injection, serum levels of tumor necrosis factor (TNF)-alpha, a proinflammatory cytokine, and prostaglandin E(2) (PGE(2)), an immunosuppressive mediator, were higher in FOS-treated rats than in control rats. Alanine aminotransferase (ALT) activity was approximately 50% lower than in controls 24 h after LPS administration in FOS-treated rats, suggesting less hepatic injury; this was confirmed through histological analysis. FOS treatment increased the number of large phagocytic Kupffer cells, as assessed by histological examination of the liver after colloidal carbon injection into the portal vein. Precision-cut liver slices (PCLS) from FOS-treated rats released more TNF-alpha and PGE(2) into the incubation medium than PCLS from control rats, independently of LPS challenge in vitro. This would suggest that the higher Kupffer cell phagocytic activity and secretion capacity due to FOS supplementation improve LPS clearance in liver tissue and reduce hepatocyte alterations. This study supports the hypothesis that oligofructose might decrease liver tissue injury after endotoxic shock and sepsis.