No abstract

Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are the major anions in the large intestinal lumen. They are produced from dietary fiber by bacterial fermentation and are known to have a variety of physiological and pathophysiological effects on the intestine. In the present study, we investigated the expression of the SCFA receptor, GPR43, in the rat distal ileum and colon. Expression of GPR43 was detected by reverse transcriptase/polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry. mRNA for GPR43 was detected, by RT-PCR, in extracts of the whole wall and separated mucosa from the ileum and colon and from muscle plus submucosa from the ileum, but not from muscle plus submucosa preparations from the colon. We raised a rabbit antiserum against a synthesized fragment of rat GPR43; this was specific for rat GPR43. GPR43 protein was detected by Western blot analysis in extracts of whole wall and separated mucosa, but not in muscle plus submucosa extracts. By immunohistochemistry, GPR43 immunoreactivity was localized to enteroendocrine cells expressing peptide YY (PYY), whereas 5-hydroxytryptamine (5-HT)-immunoreactive (IR) enteroendocrine cells were not immunoreactive for GPR43. Mast cells of the lamina propria expressing 5-HT were also GPR43-IR. The results of the present study suggest that the PYY-containing enteroendocrine cells and 5-HT-containing mucosal mast cells sense SCFAs via the GPR43 receptor. This is consistent with physiological data showing that SCFAs stimulate the release of PYY and 5-HT from the ileum and colon.

Nesfatin-1 is a novel satiety molecule in the hypothalamus and is also present in peripheral tissues. Here we sought to identify the active segment of nesfatin-1 and to determine the mechanisms of its action after peripheral administration in mice. Intraperitoneal injection of nesfatin-1 suppressed food intake in a dose-dependent manner. Nesfatin-1 has three distinct segments; we tested the effect of each segment on food intake. Injection of the midsegment decreased food intake under leptin-resistant conditions such as db/db mice and mice fed a high-fat diet. After injection of the midsegment, expression of c-Fos was significantly activated in the brainstem nucleus tractus solitarius (NTS) but not in the hypothalamic arcuate nucleus; the nicotinic cholinergic pathway to the NTS contributed to midsegment-induced anorexia. Midsegment injection significantly increased expression of proopiomelanocortin and cocaine- and amphetamine-regulated transcript genes in the NTS but not in the arcuate nucleus. Investigation of mutant midsegments demonstrated that a region with amino acid sequence similarity to the active site of agouti-related peptide was indispensable for anorexigenic induction. Our findings indicate that the midsegment of nesfatin-1 causes anorexia, possibly by activating POMC and CART neurons in the NTS via a leptin-independent mechanism after peripheral stimulation.

No abstract

Although dense animal communities at hydrothermal vents and cold seeps rely on symbioses with chemoautotrophic bacteria [1, 2], knowledge of the mechanisms underlying these chemosynthetic symbioses is still fragmentary because of the difficulty in culturing the symbionts and the hosts in the laboratory. Deep-sea Calyptogena clams harbor thioautotrophic bacterial symbionts in their gill epithelial cells [1, 2]. They have vestigial digestive tracts and nutritionally depend on their symbionts [3], which are vertically transmitted via eggs [4]. To clarify the symbionts' metabolic roles in the symbiosis and adaptations to intracellular conditions, we present the complete genome sequence of the symbiont of Calyptogena okutanii. The genome is a circular chromosome of 1,022,154 bp with 31.6% guanine + cytosine (G + C) content, and is the smallest reported genome in autotrophic bacteria. It encodes 939 protein-coding genes, including those for thioautotrophy and for the syntheses of almost all amino acids and various cofactors. However, transporters for these substances to the host cell are apparently absent. Genes that are unnecessary for an intracellular lifestyle, as well as some essential genes (e.g., ftsZ for cytokinesis), appear to have been lost from the symbiont genome. Reductive evolution of the genome might be ongoing in the vertically transmitted Calyptogena symbionts.

Short-chain fatty acids (SCFAs), including acetate, propionate and butyrate, are the most commonly found anions found in the monogastric mammalian large intestine, and are known to have a variety of physiological and pathophysiological effects on the gastrointestinal tract. We investigated the protein and mRNA expression levels of GPR41, a possible G protein coupled receptor for SCFA, using Western blot analysis and reverse transcriptase-polymerase chain reaction. We found that GPR41 protein and mRNA are expressed in human colonic mucosa. Immunohistochemistry for GPR41 showed that mucosal GPR41 protein is localized in cytoplasm of enterocytes and enteroendocrine cells. Moreover, GPR41-immunoreactive endocrine cells contained peptide YY but not serotonin or GPR43. The cellular population of GPR41 (0.01 ± 0.01 cells/crypt) was much smaller than that of GPR43 (0.33 ± 0.01 cells/crypt) in the human colon. However, the potency order of SCFA-induced phasic contraction of colonic smooth muscle that we previously reported is consistent with GPR41 (propionate ≧ butyrate > acetate) but not GPR43 (propionate = butyrate = acetate). Therefore, the present study suggests that GPR41 expressed in human colonic mucosa may function as a sensor for luminal SCFAs.Short-chain fatty acids (SCFA) are a major anion present in the large intestinal lumen of monogastric mammals including humans. SCFAs are produced during anaerobic bacterial fermentation of unabsorbed carbohydrates and dietary fibers. The concentration of SCFAs in human feces is reported to be approximately 100 mM, and are primarily comprised of acetate, propionate, and butyrate. Molar ratios of SCFAs in human fecal content are 50-60, 15-20, and 10-20 for acetate, propionate, and butyrate respectively (3, 22). Through absorption and metabolism of SCFAs, the host is able to salvage energy from food not digested in the upper intestine. Furthermore, luminal SCFAs have various physiological and pathophysiological effects in the gastrointestinal (GI) tract (4,10,17,19). In our previous studies, we demonstrated that SCFAs evoke two different effects on rat colonic smooth muscle in vitro (13)(14)(15). In the early phase, propionate and butyrate induced concentrationdependent phasic contractions in circular and longitudinal muscle, but acetate had no such effect (13-15). In the late phase, propionate induced a concentration-dependent increase in frequency of spontaneous contractions in circular (13) and longitudinal muscle (15), but butyrate did not affect the frequency of spontaneous longitudinal muscle contractions (15). On the other hand, acetate induced a

Biotechnology advances have provided novel methods for the risk assessment of chemicals. The application of microarray technologies to toxicology, known as toxicogenomics, is becoming an accepted approach for identifying chemicals with potential safety problems. Gene expression profiling is expected to identify the mechanisms that underlie the potential toxicity of chemicals. This technology has also been applied to identify biomarkers of toxicity to predict potential hazardous chemicals. Ultimately, toxicogenomics is expected to aid in risk assessment. The following discussion explores potential applications and features of the Japanese Toxicogenomics Project.

It was found that uraemic toxin, p-cresol, was associated with constipation and that SYN treatment resulted in normalization of bowel habits and a decrease of serum p-cresol levels in HD patients. Therefore, SYN treatment may be anticipated to reduce the toxic effect of p-cresol in HD patients.