Food-induced changes of lipids in rat neuronal tissue visualized by ToF-SIMS imaging.

Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to image the lipid localization in brain tissue sections from rats fed specially processed cereals (SPC). An IonTof 5 instrument equipped with a Bi cluster ion gun was used to analyze the tissue sections. Data from 15 brain samples from control and cereal-fed rats were recorded and exported to principal components analysis (PCA). The data clearly show changes of certain lipids in the brain following cereal feeding. PCA score plots show a good separation in lipid distribution between the control and the SPC-fed group. The loadings plot reveal that the groups separated mainly due to changes in cholesterol, vitamin E and c18:2, c16:0 fatty acid distribution as well as some short chain monocarboxylic fatty acid compositions. These insights relate to the working mechanism of SPC as a dietary supplement. SPC is thought to activate antisecretory factor (AF), an endogenous protein with regulatory function for inflammation and fluid secretion. These data provide insights into lipid content in brain following SPC feeding and suggest a relation to activating AF.

Specially processed cereals diet increases plasma levels of active antisecretory factor and up-regulates rat hepatic glutathione S-transferase mu.

OBJECTIVE: Antisecretory factor (AF) inhibits pathologic fluid secretion and inflammation. AF is expressed in most tissues and is secreted into the blood. Challenge with bacterial enterotoxins increases AF activity. The plasma level of active AF is also increased after intake of certain food constituents, such as specially processed cereals, SPC. The exact molecular events that mediate these responses have remained obscure. The objective of this study was to investigate changes in protein expression in liver after SPC diet. METHODS: Rats were fed SPC or standard rodent diet for 18 d. The induction of AF in plasma was tested by ELISA. Changes in the liver proteome were analyzed by using 2D DIGE and LC-MS/MS. Further characterizations were done with Western blot and immunohistochemistry studies. RESULTS: The AF activity was increased after intake of SPC. Equivalent to recombinant AF, 6.6 ± 1.09 ng/well could be detected in control plasma compared to 26 ± 5.73 ng/well in plasma after SPC treatment. We found that the protein level of glutathione S-transferase mu (GST mu) was significantly up-regulated 1.2-fold in rat liver after stimulation with SPC (wheat). The result was further confirmed by Western blot analysis. Immunohistochemistry showed staining for GST mu1 and AF preferentially in the central parts of the liver lobuli. CONCLUSION: Given the known role of GST mu1 in inducing defense, our results suggest that SPC-induced GST mu1 up-regulation can contribute to the positive clinical effects seen by SPC treatment.

Food-induced antisecretory factor activity is correlated with small bowel length in patients with intestinal resections.

Specially processed cereals (SPC) can increase antisecretory factor (AF) activity in humans with an intact intestine. The aim of the present study was to investigate whether AF synthesis could be induced in patients who had been subjected to intestinal resections. Eight patients with varying extents of intestinal resections due to Crohn's disease and six healthy controls participated. All subjects received 54 g SPC daily for 2 weeks. Plasma AF activity was determined before, during and after the treatment period. Baseline diet and medications were kept unchanged. The patients registered the daily number of bowel movements. The SPC diet increased AF activity in all controls. In the patients there was a significant correlation between the length of the remaining small intestine and AF induction (r=0.94, p<0.01) and only those patients with a remaining small intestine of about 3 m reached AF values comparable to those in healthy subjects. It is concluded that small bowel length is related to the ability of humans to induce AF activity by dietary means.

Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats.

OBJECTIVES: Severe postnatal infection leads to a systemic inflammatory response with release of cytokines and glucocorticoids, representing a stressful event for the newborn child. The purpose of this study was to mimic this situation and to study the effects of early postnatal endotoxin exposure of female rat pups on metabolic, endocrine and anthropometric variables in adulthood. DESIGN: Female pups were given subcutaneous injections of lipopolysaccharides (LPS; Salmonella enteriditis, 0.05 mg/kg) or vehicle 3 and 5 days after birth. RESULTS: Six hours after injection, LPS-treated rats had higher corticosterone levels than controls. As adults, LPS-exposed female rats showed increased insulin sensitivity (P<0.05), measured with the hyperinsulinemic euglycemic clamp (5 mU/kg per min). They exhibited a higher locomotor activity (P<0.05) and increased skeletal muscle mass in comparison with controls (P<0.05). Basal ACTH and corticosterone levels in LPS-treated rats were elevated (P<0.05), as were corticosterone levels after exposure to a novel environment stress (P<0.05). The adrenals were morphologically changed and enlarged (P<0.05) in LPS-exposed rats at 11 weeks of age, and a higher density of hypothalamic but not hippocampal glucocorticoid receptor protein was found in the LPS-treated rats (P<0.05). Furthermore, circulating progesterone levels were lower (P<0.05) and testosterone tended to be higher. CONCLUSION: The results indicate that postnatal exposure to LPS leads to increased insulin sensitivity in the adult female rat. In addition, LPS-treated rats showed changes in the regulation of hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes. This study suggests that postnatal exposure to an endotoxin such as LPS can induce specific programming of neuroendocrine regulation, with long-term consequences in adult life.