The evidence of apelin has the bidirectional effects on feeding regulation in Siberian sturgeon (Acipenser baerii)

Apelin is a peptide, mainly produced in the brain, which participates in several physiologic effects. However, knowledge about the mechanism of appetite regulation in teleosts, including the role of apelin is not well understood. The aim of this study is to explore the effect of feeding status on the expression of apelin mRNA in the whole brain and the effects of injection of apelin on food intake in Siberian sturgeon (Acipenser baerii). In this study, we first cloned the apelin cDNA sequence of the Siberian sturgeon. We obtained a 1046-bp cDNA fragment, including a 237-bp open reading frame (ORF) that encoded 78 amino acids. Apelin was widely distributed in 11 tissues related to feeding regulation, with the highest expression in thewhole brain, followed by the spleen and trunk kidney. In addition, we measured the effects of periprandial (preprandial and postprandial) change, fasting and re-feeding on apelin mRNA expression in whole brain. The level of apelin mRNA was significantly decreased 1 h after feeding. The results of the fasting experiment showed that the expression of apelin mRNA in the brain was significantly reduced after 1 day of fasting but consistently increased throughout the 15-day food deprivation period. When the 15-day fasted fish were re-fed, apelin mRNA expression in the brain was significantly increased as compared to that of the control. These results suggest that apelin may play a bidirectional role in the regulation of food intake in the Siberian sturgeon. In order to further examine the effect of apelin on feeding regulation in Siberian sturgeons, acute and chronic intraperitoneal (i.p.) injection experiments were performed and food intakes were recorded. Results showed that acute i.p. injection of apelin-13 reduced food intake, however, chronic i.p. injection apelin-13 increased the food intake for 7 days in Siberian sturgeons. In conclusion, our results show that apelin has a bidirectional effect on feeding regulation in Siberian sturgeons by acting as a satiety factor in short-term feeding regulation and a starvation factor in long-term feeding regulation.     

Cloning of Wap65 in sea bass (Dicentrarchus labrax) and sea bream (Sparus aurata) and expression in sea bass tissues

The complementary DNA encoding WAP65 protein was cloned from the liver of two fish species sea bass (Dicentrarchus labrax) and sea bream (Sparus aurata). Full-length cDNA sequences were obtained from reverse transcribed total RNA, followed by 5′ and 3′ rapid amplification of cDNA end (RACE) experiments. The full-length cDNA sequence of D. labrax is 1709 bp and the coding sequence is flanked by a 67 bp 5′-UTR and a 358 bp 3′-UTR. The full-length cDNA sequence of S. aurata is 1599 bp, and the coding sequence is flanked by a 48 bp 5′-UTR and a 273 bp 3′-UTR. The deduced amino acid putative primary sequences are composed of 427 and 425 amino acid residues for D. labrax and S. aurata, respectively. They display high homologies with previously described fish WAP65 and other hemopexin-like proteins from rabbit (Oryctolagus cuniculus). Expression of Wap65 has proved to be a natural physiological adaptive answer of teleost fish to warm temperature acclimation. In all fish species studied to date, Wap65 was found expressed mainly by the liver, although other tissues seem able to express Wap65 in response to a warm temperature acclimation, in a specie specific manner. Here, we investigate the tissue specific expression of Wap65 in D. labrax and S. aurata in response to a warm temperature acclimation, by RT-PCR analysis.     

PYY(3-36) into the arcuate nucleus inhibits food deprivation-induced increases in food hoarding and intake

Central administration of neuropeptide Y (NPY) increases food intake in laboratory rats and mice, as well as food foraging and hoarding in Siberian hamsters. The NPY-Y1 and Y5 receptors (Rs) within the hypothalamus appear sufficient to account for these increases in ingestive behaviors. Stimulation of NPY-Y2Rs in the Arcuate nucleus (Arc) has an anorexigenic effect as shown by central or peripheral administration of its natural ligand peptide YY (3-36) and pharmacological NPY-Y2R antagonism by BIIE0246 increases food intake. Both effects on food intake by NPY-Y2R agonism and antagonism are relatively short-lived lasting ∼4 h. The role of NPY-Y2Rs in appetitive ingestive behaviors (food foraging/hoarding) is untested, however. Therefore, Siberians hamsters, a natural food hoarder, were housed in a semi-natural burrow/foraging system that had (a) foraging requirement (10 revolutions/pellet), no free food (true foraging group), (b) no running wheel access, free food (general malaise control) or (c) running wheel access, free food (exercise control). We microinjected BIIE0246 (antagonist) and PYY_(3-36) (agonist) into the Arc to test the role of NPY-Y2Rs there on ingestive behaviors. Food foraging, hoarding, and intake were not affected by Arc BIIE0246 microinjection in fed hamsters 1, 2, 4, and 24 h post injection. Stimulation of NPY-Y2Rs by PYY_(3-36) inhibited food intake at 0–1 and 1–2 h and food hoarding at 1–2 h without causing general malaise or affecting foraging. Collectively, these results implicate a sufficiency, but not necessity, of the Arc NPY-Y2R in the inhibition of food intake and food hoarding by Siberian hamsters.     

Expression of allograft inflammatory factor-1 (AIF-1) in response to bacterial challenge and tissue injury in the pearl oyster,Pinctada martensii

Allograft inflammatory factor-1 (AIF-1), an interferon (IFN)-γ-inducible calcium-binding cytokine, is associated with the inflammatory response and defense. We cloned and analyzed the expression pattern of the AIF-1 gene of the pearl oyster Pinctada martensii, hereafter designated PmAIF-1. The full-length PmAIF-1 cDNA is 946 bp in length and consists of a 5′-untranslated region (UTR) of 120 bp, a 3′-UTR of 376 bp, and an open reading frame (ORF) of 450 bp encoding a polypeptide of 149 amino acids with an estimated molecular mass of 17 kDa. Sequence analysis reveals that PmAIF-1 contains two EF hand Ca⁺²-binding motifs like those in previously characterized AIF-1s while alignment with known AIF-1 protein sequences reveals higher similarity to invertebrate orthologs than to those of vertebrates.Quantitative PCR analysis reveals that PmAIF-1 is constitutively expressed, with the highest expression detected in hemocytes, and the expression level of PmAIF-1 mRNA was significantly up-regulated in hemocytes, gill, digestive gland under bacterial challenge and tissue injury. After challenged by gram-negative bacteria Vibrio alginolyticus and Vibrio parahaemolyticus, gram-positive bacteria Bacillus subtilis, the expression level of this gene in hemocytes were all up-regulated and reached the maximum point at 12 h (5.80 folds, P < 0.01), 6 h (5.02 folds, P < 0.01) and 12 h (5.49 folds, P < 0.01), respectively. Under shell damage and mantle injury, PmAIF-1 mRNA increased gradually in the first 3 h and reached a peak of expression at 6 h post-injury. These findings suggest that PmAIF-1 is an acute-response protein involved in the innate immune responses of pearl oysters, and provide general information about the mechanisms of innate immune defense against bacterial infection in pearl oysters.     

Digestive capacities allow the Mexican long-nosed bat (Leptonycteris nivalis) to live in cold environments

Digestive capabilities of nectar-feeding vertebrates to assimilate sugars affect their ability to acquire and store energy and could determine the minimal temperatures at which these animals can survive. Here, we described the sugar digestive capability of Leptonycteris nivalis and related it with its capacity to live in cold environments. We measured the enzymatic activity, food intake rate and changes in body mass of bats feeding at four different sucrose concentrations (from 5 to 35% wt./vol.). Additionally, we used a mathematical model to predict food intake and compared it with the food intake of bats. L. nivalis was able to obtain ~ 111.3 kJ of energy regardless of the sugar concentration of their food. Also, bats gained ~ 2.57 g of mass during the experimental trials and this gain was independent of sugar concentration. The affinity (1 / K_m) of sucrase (EC 3.2.1.48) was one order of magnitude higher relative to that reported for its sister species Leptonycteris yerbabuenae (0.250 and 0.0189 mmol^? 1 L, respectively), allowing this species to have a higher energy intake rate. We propose that the high ability to acquire energy conferred L. nivalis the faculty to invade cold environments, avoiding in this way the ecological competition with its sympatric species L. yerbabuenae.     

Influence of environmental related concentrations of heavy metals on motility parameters and antioxidant responses in sturgeon sperm

The effects of heavy metals (Cd, Cr and Cd + Cr) on the motility parameters and oxidative stress of sterlet (Acipenser ruthenus) sperm were investigated in vitro. Sturgeon sperm were exposed for 2 h to heavy metals at environmental related concentrations (0.1 mg L^?1 Cr, 0.001 mg L^?1 Cd, 0.1 mg L^?1 Cr + 0.001 mg L^?1 Cd) and higher concentrations (5.0 mg L^?1 Cr, 0.05 mg L^?1 Cd, 5.0 mg L^?1 Cr + 0.05 mg L^?1 Cd). Results revealed that environmental concentrations of heavy metals had no significant influence on motility parameters and antioxidant responses indices in sturgeon sperm, except for LPO level and SOD activity. But higher concentrations of these metals induced oxidative tress in sturgeon sperm in vitro, associated with sperm motility parameters inhibition. Our results suggest that using of sperm in vitro assays may provide a novel and efficiently means for evaluating the effects of residual heavy metals in aquatic environment on sturgeon.     

The CCKB antagonist CI988 reduces food intake in fasted rats via a dopamine mediated pathway

Studies have shown a reduction of food intake following peripheral and brain injection of CCK. However, it remains to be established whether endogenous central CCK is involved in the regulation of food intake. We investigated the role of central CCK in the regulation of food intake by pharmacological manipulation of the CCK_B (CCK₂) receptor system. Intracerebroventricularly (ICV) cannulated male Sprague Dawley rats were fasted for 24 h and received an ICV injection of the CCK_B receptor antagonist CI988 at a dose of 10 nmol or 49 nmol or vehicle. Another group received two consecutive ICV injections consisting of the corticotropin-releasing factor (CRF) receptor-1 (CRF₁) antagonist, CP376395 (3 nmol) or the CRF₂ receptor antagonist, K41498 (2 nmol) alone, or followed by CI988 (49 nmol). Lastly, another group of rats received an intraperitoneal (IP) injection of the dopamine antagonist, flupentixol (∼197 and ∼493 nmol/kg) alone, or followed by CI988 (49 nmol, ICV). Cumulative food intake was assessed for 11 h. Vehicle injected rats showed a robust feeding response. CI988 at 49 nmol reduced food intake by 30% starting at 2 h post injection. CP376395 and K41498 had no effect on food intake. Flupentixol injected IP at a dose of 197 and 493 nmol/kg alone did not modulate food intake whereas the higher dose blocked the CI988-induced reduction of feeding. During the dark phase, CI988 had no effect on food intake in unfasted rats. In summary, CCK_B signaling is involved in the regulation of food intake after a fast likely by downstream dopamine signaling.     

Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: A randomized clinical trial

The effects of metformin and pioglitazone on ghrelin, a physiologic regulator of appetite and food intake, have not been clearly established. In a randomized clinical trial, we randomly assigned 60 type 2 diabetic patients to either metformin (Group A; n = 30) or pioglitazone (Group B; n = 30) treatment groups. The groups were similar in their baseline characteristics. A standard fasting 75 g oral glucose tolerance test was performed at time zero before starting metformin or pioglitazone, and 3 months later. After 3 months of treatment, pioglitazone, but not metformin, was significantly associated with weight gain. Both groups experienced a significant reduction in fasting plasma glucose (p < 0.01), hemoglobin A1c (p < 0.01 in Group A and p < 0.05 in Group B), and insulin resistance (p < 0.01). The effect of metformin on preprandial ghrelin and its response to glucose challenge was not significant, while the pioglitazone group had a significant reduction in preprandial ghrelin levels after treatment (p < 0.05). The effect of pioglitazone on ghrelin was independent of changes in body weight, body mass index, glucose control, insulin resistance, and plasma insulin. In conclusion, treatment with pioglitazone is associated with a decrease in preprandial ghrelin levels and therefore, the weight gain and increased food intake related to pioglitazone use cannot be explained by its effects on ghrelin. The effect of pioglitazone on ghrelin is independent of changes in body weight, body mass index, plasma insulin, insulin resistance, or glucose control.     

Metabolic effect of short term administration of Hoodia gordonii,an herbal appetite suppressant

Hoodia gordonii (family: Apocynaceae) is used traditionally by the Khoi-San tribes to control hunger. It has become extremely popular and has triggered commercial interest due to its appetite suppressant property. The present study was undertaken to investigate the appetite regulatory mechanism and associated metabolic changes induced by the herb. Effect of organic solvent extract of H. gordonii on food intake and body weight of male Sprague Dawley rats was monitored at three different doses 50, 100 and 150 mg/kg body weight, given orally for five days. Subsequently, the dose of 100 mg/kg body weight was selected for further studies on the regulatory hormones and biochemical variables. Dose-dependent reduction in food intake (12–26%) was observed at a dose of 100 and 150 mg/kg body weight (p < 0.05). Appetite suppression persisted for 6 h and food intake was restored within 24 h after stopping of the treatment. There was an increase in liver glycogen stores, activity of mitochondrial CPT-1 and thyroid hormones in treated animals. The circulating levels of NPY and IGF-1 were decreased with marginal increase in leptin and CCK, in case of treated rats. There was no change in blood glucose and insulin levels were not affected significantly. The hormonal and metabolic changes due to treatment with the H. gordonii extract may be responsible for its anorectic activity.     

Cloning and sequencing of three new putative toxin genes from Clostridium bifermentans CH18

Three new open reading frames were found downstream from cbm71, a toxin gene from Clostridium bifermentans malaysia (Cbm) strain CH18. The first one (91 bp downstream) called cbm72, is 1857 bp long and encodes a 71 727-Da protein (Cbm72) with a sequence similar to that of Bacillus thuringiensis delta-endotoxins. This protein shows no significant toxicity to mosquito larvae. The two others, cbm17.1 (462 bp) and cbm17.2 (459 bp), are copies of the same gene encoding Cbm P18 and P16 polypeptides and located 426 bp and 1022 bp downstream from cbm72, respectively. They encode 17 189-Da and 17 451-Da proteins with sequences 44.6% similar to that of Aspergillus fumigatus hemolysin; however, they were not hemolytic in the conditions tested.     

Associations between flavan-3-ol intake and CVD risk in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk)

Dietary intervention studies suggest that flavan-3-ol intake can improve vascular function and reduce the risk of cardiovascular diseases (CVD). However, results from prospective studies failed to show a consistent beneficial effect. Associations between flavan-3-ol intake and CVD risk in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) were investigated. Data were available from 24,885 (11,252 men; 13,633 women) participants, recruited between 1993 and 1997 into the EPIC-Norfolk study. Flavan-3-ol intake was assessed using 7-day food diaries and the FLAVIOLA Flavanol Food Composition database. Missing data for plasma cholesterol and vitamin C were imputed using multiple imputation. Associations between flavan-3-ol intake and blood pressure at baseline were determined using linear regression models. Associations with CVD risk were estimated using Cox regression analyses. Median intake of total flavan-3-ols was 1034 mg/d (range: 0–8531 mg/d) for men and 970 mg/d (0–6695 mg/d) for women, median intake of flavan-3-ol monomers was 233 mg/d (0–3248 mg/d) for men and 217 (0–2712 mg/d) for women. There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure (BP). After 286,147 person-years of follow-up, there were 8463 cardiovascular events and 1987 CVD related deaths; no consistent association between flavan-3-ol intake and CVD risk (HR 0.93, 95% CI: 0.87; 1.00; Q1 vs Q5) or mortality was observed (HR 0.93, 95% CI: 0.84; 1.04). Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk.     

Ghrelin and glucagon-like peptide-2 increase immediately following massive small bowel resection

Children with short bowel syndrome face life-threatening complications. Therefore, there is an urgent need for a new therapy to induce effective adaptation of the remnant intestine. Adaptation occurs only during feeding. We focused on preprandial acyl ghrelin and des-acyl ghrelin, and postprandial glucagon-like peptide-2 (GLP-2), which are known to have active orexigenic and trophic actions. This study aims to clarify the secretion trends of these hormones after massive small bowel resection and to obtain basic data for developing a new treatment. Sixty-three growing male rats were used: 3 were designated as controls receiving no operation and 60 were randomized into the 80% small bowel resection (80% SBR) group and the transection and re-anastomosis group. Changes in body weight, food intake, and remnant intestine morphology were also assessed for 15 days after the operation. Acyl ghrelin and des-acyl ghrelin levels increased immediately, equivalently in both operation groups (P = 0.09 and 0.70). Interestingly, in 80% SBR animals, des-acyl ghrelin peaked on day 1 and acyl ghrelin peaked on day 4 (P = 0.0007 and P = 0.049 vs controls). GLP-2 secretion was obvious in 80% SBR animals (P = 2.25 × 10⁻⁶), which increased immediately and peaked on day 4 (P = 0.009 vs. controls). Body weight and food intake in 80% SBR animals recovered to preoperative levels on day 4. Morphological adaptations were evident after day 4. Our results may suggest a management strategy to reinforce these physiological hormone secretion patterns in developing a new therapy for short bowel syndrome.     

Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats

Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9 mg/kg BW for 6 weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3 weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet for the last 3 weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay kits. Plasma and liver tissue levels of XN and its metabolites were determined by liquid–chromatography tandem mass spectrometry. Plasma and liver tissue levels of xanthohumol were similar between low and medium dose groups and significantly (p < 0.05) elevated in the highest dose group. There was a dose-dependent effect on body weight and plasma glucose levels. The highest dose group (n = 6) had significantly lower plasma glucose levels compared to the control group (n = 6) in male but not female rats. There was also a significant decrease in body weight for male rats in the highest dose group (16.9 mg/kg BW) compared to rats that received no xanthohumol, which was also not seen for female rats. Plasma cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not affected by treatment. The findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome.     

Synthesis and SAR of derivatives based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity

This Letter describes a series of potent and selective BRS-3 agonists containing a biarylethylimidazole pharmacophore. Extensive SAR studies were carried out with different aryl substitutions. This work led to the identification of a compound 2-{2-[4-(pyridin-2-yl)phenyl]ethyl}-5-(2,2-dimethylbutyl)-1H-imidazole 9 with excellent binding affinity (IC₅₀ = 18 nM, hBRS-3) and functional agonist activity (EC₅₀ = 47 nM, 99% activation). After oral administration, compound 9 had sufficient exposure in diet induced obese mice to demonstrate efficacy in lowering food intake and body weight via BRS-3 activation.     

Effects of total nonstructural carbohydrates and nitrogen balance on voluntary intake of goats and digestibility of gamagrass hay harvested at sunrise and sunset

We evaluated differences in composition of Iuka gamagrass (Tripsacum dactyloides L.) hay harvested at 06:00 (AM harvest) or 18:00 h (PM harvest), and measured how protein supplementation and time of harvest interact to affect the voluntary intake, digestibility, and N balance of goats. Boer cross wethers (n = 28; 24 kg) were randomly assigned to be fed supplement (310 g/kg of crude protein (CP), fed at 110 g/kg of dry matter (DM) intake, 14 goats) or no supplement (14 goats). Within supplemented or not supplemented groups, goats were randomly assigned to a crossover design of AM harvest (seven goats) or PM harvest (seven goats), and housed individually in metabolism crates with free access to water and mineral blocks. They were fed twice daily, with supplement offered 30 min prior to the morning feedings. After a 7-d adaptation, voluntary intake (goats were offered 1100 g/kg of previous day's intake) was measured for 14 d, followed by a 4-d adjustment phase to equalize DM offered between periods, and finally a 5-d digestion and balance phase. After Period 1, goats were switched to their new hay harvest times, and the protocol was repeated. Compared to the AM harvest, the PM harvest had higher (P<0.03) proportions of total nonstructural carbohydrates (TNC, 70.8 g/kg DM versus 59.0 g/kg DM), monosaccharides (37.0 g/kg DM versus 28.6 g/kg DM), di- and polysaccharides (18.5 g/kg DM versus 15.4 g/kg DM) and less neutral detergent fiber (NDF, 700 g/kg versus 710 g/kg). Crude protein (79 g/kg DM) and starch (15.2 g/kg DM) were similar for the PM and AM harvest. Dry matter digestibility was higher (P<0.03) for the PM versus AM harvests (555 g/kg DM versus 531 g/kg DM) and for supplemented versus not supplemented (563 g/kg DM versus 522 g/kg DM). Voluntary gamagrass DM intake (550 g/d versus 548 g/d) and calculated total digestible DM intake (327 g/d versus 313 g/d) were similar for the PM and AM harvest. However, total digestible DM intake during the digestion and balance phase was higher (P<0.01) for the PM versus AM harvest (317 g/d versus 299 g/d). Time of harvest did not affect N intake, digestion, or calculated retention. Compared to no supplementation, the supplement improved (P<0.01) N digestion (6.1 g/d versus 3.7 g/d) and retention (2.2 g/d versus 1.1 g/d). The PM harvest increased DM digested, largely TNC and digestible DM intake by goats due to increased TNC and not because of a 2% increase in DM intake. Providing a protein supplement had very limited effects on intake and digestibility of gamagrass.