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Biomedical subjects

Akio Inui

Publications and source records attributed to Akio Inui.

At least 19 recordsLinked to original sources
PubMed2003

Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats.

Ghrelin is a newly discovered orexigenic peptide originating from the stomach. However, its action in regulating the fed and fasted motor activity of the digestive tract is not fully understood. In the present study, we examined the effects of intracerebroventricular (I.C.V.) and intravenous (I.V.) injection of ghrelin on the physiological fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. I.C.V. and I.V. injection of ghrelin induced fasted motor activity in the duodenum in normal fed rats, while I.V. injection of ghrelin induced fasted motor activity in both the stomach and duodenum in vagotomized rats. The effects of I.C.V. and I.V. injected ghrelin were blocked by growth hormone secretagogue receptor (GHS-R) antagonist given by the same route and also blocked by immunoneutralization of neuropeptide Y (NPY) in the brain. The effects of I.V. injected ghrelin were not altered by I.C.V. injection of GHS-R antagonist in vagotomized rats. Injection of GHS-R antagonist blocked the fasted motor activity in both the stomach and duodenum in vagotomized rats but did not affect the fasted motor activity in normal rats. Low intragastric pH inhibited the effect of ghrelin. The present results indicate that ghrelin is involved in regulation of fasted motor activity in the stomach and duodenum. Peripheral ghrelin may induce the fasted motor activity by activating the NPY neurons in the brain, probably through ghrelin receptors on vagal afferent neurons. Once the brain mechanism is eliminated by truncal vagotomy, ghrelin might be primarily involved in the regulation of fasted motor activity through ghrelin receptors on the stomach and duodenum. The action of ghrelin to induce fasted motor activity is strongly affected by intragastric pH; low pH inhibits the action.

Animals↗
PubMed2003

Characterization of the effects of pancreatic polypeptide in the regulation of energy balance.

BACKGROUND & AIMS: Pancreatic polypeptide (PP) belongs to a family of peptides including neuropeptide Y and peptide YY. We examined the role of PP in the regulation of body weight as well as the therapeutic potential of PP. METHODS: We measured food intake, gastric emptying, oxygen consumption, and gene expression of hypothalamic neuropeptides, gastric ghrelin, and adipocytokines in mice after administering PP intraperitoneally. Peptide gene expression was also examined in PP-overexpressing mice. Vagal and sympathetic nerve activities were recorded after intravenous administration in rats. Effects of repeated administrations of PP on energy balance and on glucose and lipid metabolism were examined in both ob/ob obese mice and fatty liver Shionogi (FLS)-ob/ob obese mice. RESULTS: Peripherally administered PP induced negative energy balance by decreasing food intake and gastric emptying while increasing energy expenditure. The mechanism involved modification of expression of feeding-regulatory peptides (decrease in orexigenic neuropeptide Y, orexin, and ghrelin along with an increase in anorexigenic urocortin) and activity of the vagovagal or vagosympathetic reflex arc. PP reduced leptin in white adipose tissue and corticotropin-releasing factor gene expression. The expression of gastric ghrelin and hypothalamic orexin was decreased in PP-overexpressing mice. Repeated administrations of PP decreased body weight gain and ameliorated insulin resistance and hyperlipidemia in both ob/ob obese mice and FLS-ob/ob obese mice. Liver enzyme abnormalities in FLS-ob/ob obese mice were also ameliorated by PP. CONCLUSIONS: These observations indicate that PP may influence food intake, energy metabolism, and the expression of hypothalamic peptides and gastric ghrelin.

Animals↗
PubMed2003

Obesity--a chronic health problem in cloned mice?

The majority of cloned animals derived by nuclear transfer die during gestation and display neonatal abnormalities. However, because of the long generation interval of cloned animal species, the long-term consequences of cloning on health have been difficult to access. Recent studies in mice have provided evidence that cloned animals might have chronic health problems such as obesity. Obesity in cloned mice is likely to reflect epigenetic abnormalities that arise partly from inadequate nuclear programming; these obese mice display a unique phenotype that is suggestive of a defect other than malfunction of the leptin-melanocortin system, which occurs in most rodent models of obesity and in human obesity.

Animals↗
PubMed2003

Is obesity an inflammatory disease?

BACKGROUND: Most obese individuals have elevated concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), markers of inflammation closely associated with diabetes, hypertension, and stroke. HYPOTHESIS: Obesity is a low-grade inflammatory disease, and Roux-en-Y gastric bypass (RYGB) reduces biochemical markers of inflammation and modifies gene expression in hypothalamic food intake/energy-related nuclei and subcutaneous abdominal fat (SAF). METHODS: Obesity was induced in 24 3-week-old Sprague Dawley pups fed a high-energy diet (HED). Three groups (n = 8/group) were studied: RYGB, sham-operated pair-fed, and sham-operated ad libitum HED. Controls were nonobese rats fed chow (n = 6). Rats were killed 10 days after operation, and blood was collected to measure corticosterone and SAF and mesenteric fat to measure IL-6, TNF-alpha, and corticosterone. Total mRNA from arcuate nucleus and SAF purified for gene expression profiling. Data were analyzed with analysis of variance, Mann-Whitney test, and t test. RESULTS: Before operation, the body weight of the obese groups was 493 +/- 7 g and control = 394 +/- 12g. The 10-day postoperative weight was RYGB = 417 +/- 21 g, pair-fed = 436 +/- 14 g, and ad libitum HED = 484 +/- 15 g. Mesenteric and SAF weight decreased in RYGB. Mesenteric/SAF ratio of IL-6, TNF-alpha, corticosterone, and gene profiling showed decrease of inflammation after RYGB. CONCLUSIONS: Gastric bypass reduces biochemical markers of inflammation, suggesting that obesity is an inflammatory condition.

Adipose Tissue↗
PubMed2003

Cachexia and obesity: two sides of one coin?

PURPOSE OF REVIEW: Leptin, a member of the interleukin-6 superfamily of proteins, modifies the gene expression and synthetic pathway of both orexigenic (appetite-stimulating) and anorexigenic (appetite-suppressing) molecules in the hypothalamus, thereby controlling adipocyte energy stores. Lack of leptin secretion or the inability of leptin to interact with these molecules via leptin receptors, prevent leptin's effects and lead to obesity. It is not well known, however, how these feeding-regulatory molecules are affected in cachexia associated with cancer and other critical conditions in which cytokines such as interleukin-1 and interleukin-6 may have a key role. RECENT FINDINGS: Decreased leptin and increased leptin-like signaling by cytokines in the hypothalamus are the hallmark of obesity and cachexia, respectively. Increased orexigenic and impaired anorexigenic signaling produces hyperphagia and obesity, while the reverse applies to anorexia-cachexia in which adaptive feeding response to starvation is lacking or insufficient. SUMMARY: Imbalanced operation of orexigenic and anorexigenic circuits perturbs the homeostatic loop of body weight regulation leading to either obesity or cachexia. Modifiers of the central effects on appetite and energy metabolism could restore the balance and be effective for treating both conditions. In cachexia this may especially be true when combined with agents that target muscle and protein breakdown.

Anorexia↗
PubMed2003

Synergistic effects of Y2 and Y4 receptors on adiposity and bone mass revealed in double knockout mice.

Neuropeptide Y regulates numerous physiological processes via at least five different Y receptors, but the specific roles of each receptor are still unclear. We previously demonstrated that Y2 receptor knockout results in a lean phenotype, increased cancellous bone volume, and an increase in plasma pancreatic polypeptide (PP), a ligand for Y4 receptors. PP-overexpressing mice are also known to have a lean phenotype. Deletion of the Y4 receptor also produced a lean phenotype and increased plasma PP levels. We therefore hypothesized that part of the Y2 phenotype results from increased PP action on Y4 receptors and tested this in PP transgenic Y4(-/-) and Y2(-/-) Y4(-/-) double knockout mice. Bone mass was not altered in Y4 knockout mice. Surprisingly, despite significant hyperphagia, Y2(-/-) Y4(-/-) mice retained a markedly lean phenotype, with reduced body weight, white adipose tissue mass, leptinemia, and insulinemia. Furthermore, bone volume was also increased threefold in Y2(-/-) Y4(-/-) mice, and this was associated with enhanced osteoblastic activity. These changes were more pronounced than those observed in Y2(-/-) mice, suggesting synergy between Y2 and Y4 receptor pathways. The lack of bone changes in PP transgenic mice suggests that PP alone is not responsible for the bone mass increases but might play a major role in the lean phenotype. However, a synergistic interaction between Y2 and Y4 pathways seems to regulate bone volume and adiposity and could have important implications for possible interventions in obesity and for anabolic treatment of osteoporotic bone loss.

Animals↗
PubMed2003

Serotonin stimulates endotoxin translocation via 5-HT3 receptors in the rat ileum.

Because few previous studies have investigated the mechanisms of endotoxin translocation induced by intestinal obstruction, we aimed to clarify whether or not serotonin [5-hydroxytryptamine (5-HT)], which is released from enterochromaffin (EC) cells, is responsible for alterations of the mucosal permeability to endotoxin and to identify the 5-HT receptor subtypes that mediate this action. FITC-labeled LPS (FITC-LPS) was injected into the ileum of rats, and the FITC-LPS level in the superior mesenteric vein was subsequently measured by using a fluorescence spectrophotometer. To measure the 5-HT release induced by high intraluminal pressure, ex vivo preparation of vascularly and luminally perfused rat ileum was used. Results demonstrated that elevated intraluminal pressure stimulates the translocation of FITC-LPS and the release of 5-HT from the EC cells into the intestinal lumen but not into the portal circulation. This FITC-LPS translocation, which was stimulated by exogenously applied 5-HT in the lumen and the jugular vein, was inhibited by 5-HT(3) receptor antagonist administration both intaluminally and intravenously. The stimulatory effect of elevated intraluminal pressure on the translocation of FITC-LPS was inhibited by the intraluminal and intravenous administration of 5-HT(3) receptor antagonist. These results suggest that 5-HT released from EC cells may be involved in the translocation of FITC-LPS induced by elevated intraluminal pressure and that this effect is mediated by 5-HT(3) receptors that may be located in the intestinal epithelium.

Animals↗
PubMed2003

Orexigenic/anorexigenic signals in bulimia nervosa.

Bulimia nervosa (BN) and Anorexia Nervosa (AN) are currently classified as eating disorders (ED). Both disorders are the product of complex interaction between physiological and psychological and social processes; they are characterized by abnormal eating behavior. However, patients with BN differ from AN in their nutritional state and response of treatment with serotonin-selective reuptake inhibitor (SSRI) as well as frequency of comorbidity of mood and anxiety disorders. Although biological mechanisms of both BN and AN are largely unknown, excess of both feeding-stimulatory and feeding inhibitory signaling in AN have been indicated. This report reviews data that point to the hypothesis that dysregulation of monoaminergic and new peptidergic circuitry controlling food intake and energy expenditure play a major role in the eating behavior of BN.

Alleles↗
PubMed2003

Histologic diagnosis and management of hypothalamic tumors in children by the use of newly developed flexible neuroendoscopes.

Hypothalamic tumors are difficult to treat surgically, and chemotherapy and/or radiation are given based on the histology and the neuraxis staging of the tumors. We have developed flexible neuroendoscopes (Yamadori-type 8 and 9) which have excellent image quality and maneuverability as well as capabilities for biopsy and electrocoagulative debulking of the cystic tumors. We report the successful application of the neuroendoscopes to 10 children with hypothalamic tumors diagnosed with computed tomography or magnetic resonance imaging. Histologic diagnosis was obtained from all the patients. Cystic tumors were evacuated, hydrocephalus managed with endoscopic operations, and some benign tumors were removed totally. The relatively non-invasive approach reported here would represent a significant technical advance in the diagnosis and management of hypothalamic and other ventricular tumors.

Adolescent↗
PubMed2003

Intracerebroventricular administration of NPY stimulates resistin gene expression in mice.

Resistin is thought to cause insulin resistance and link obesity to type 2 diabetes mellitus. However, little is known about the effects of neuropeptide Y (NPY) on resistin gene expression in white adipose tissue (WAT). Resistin gene expression was determined by northern blot analysis in food-deprived mice after NPY administration. Administered NPY (1 nmol/mouse) significantly increased resistin mRNA expression in WAT by 72% compared with artificial cerebrospinal fluid treated controls. These observations indicate that NPY might have a role in regulating resistin gene expression in WAT and that the novel brain-fat axis might be involved in the pathogenesis of obesity and related diseases.

Adipose Tissue↗
PubMed2003

Acute intracerebroventricular administration of either carboxyl-terminal or amino-terminal fragments of agouti-related peptide produces a long-term decrease in energy expenditure in rats.

We investigated if agouti-related peptide (AgRP), an endogenous antagonist of melanocortin receptors (MC3-R and MC4-R), effects energy expenditure in rats. Fragments of the carboxyl-terminal, AgRP (83-132), and the amino-terminals, AgRP (25-51) and AgRP (54-82), were administered intracerebroventricularly (ICV). Food intake, body weight and fat weight changes were measured 5 and/or 24 h after a single ICV injection of the fragments. Oxygen consumption and colonic temperature were measured as indices of energy expenditure, during 3 and 24 h after the ICV injections, respectively. An oral glucose tolerance test was performed 24 h after ICV AgRP (83-132) injection. Binding experiments were performed in HEK-293 cells that over-expressed human MC4-R. AgRP (83-132), but not AgRP (25-51) nor AgRP (54-82), induced a potent and long-lasting increase in the cumulative food intake. Both the carboxyl-terminal and amino-terminal AgRP fragments significantly decreased oxygen consumption and colonic temperature. Despite the absence of hyperphagia and cross-reactivities with MC4-R, AgRP (25-51) and AgRP (54-82) significantly increased body weight and epididymal/mesenteric fat weight. AgRP (83-132) did not affect glucose and insulin responses to the oral glucose tolerance test. AgRP causes a potent and long-lasting decrease in energy expenditure; an effect that is exhibited by carboxyl-terminal fragments and amino-terminal fragments that lack antagonist activity at the MC receptors. This suggests that the amino-terminal region of AgRP plays a regulatory role in energy metabolism.

Agouti-Related Protein↗
PubMed2002

Effect of amphetamine repeated treatment on the feeding behavior in neuropeptide Y-overexpressing mice.

The preset study examined the hypothesis that an increase of brain neuropeptide Y (NPY), an orexigenic peptide, might decrease the action of amphetamine (AMPH), a well-known anorectic agent. Transgenic mice overexpressing the NPY gene were used to compare with the wild-type control. AMPH-induced anorexia is documented to mediate through the release of dopamine (DA), via an activation of D(1)- and D(2)-subtype receptors, to affect the hypothalamic NPY. Thus, co-administration of D(1)/D(2) agonists was also performed to mimic the action of AMPH. The mice of NPY-overexpressing (NPY-OX) and wild-type groups were administered with AMPH or a combination of D(1)/D(2) agonists repeatedly for 5 days. We found that repeated AMPH administration-induced anorexia in wild-type mice was longer (at the initial 3 days) than that in NPY-OX mice (only at the first day). Moreover, repeated co-administration of D(1)/D(2) agonists significantly exerted a continuous anorectic effect in wild-type mice, but exerted a significant effect only at the first day in NPY-OX mice. These results indicated that the anorectic effect of AMPH decayed faster in NPY-OX mice and suggested that NPY expression by the stimuli could counteract the anorectic effect of AMPH. Thus, NPY can be considered to play a functional role in the regulation of AMPH-induced anorexia in mice.

Amphetamine↗