Minglun Tsai

Centrally administered nesfatin-1 inhibits feeding behaviour and gastroduodenal motility in mice.

Nesfatin-1 was recently identified as a peptide with anorexigenic effects that is localized in the hypothalamus and adipocytes. Not much is known about the effect of nesfatin-1 on gut motility. Food intake was measured after intracerebroventricular administration of nesfatin-1 in food-deprived mice. Antral and duodenal motility was assessed by using a manometric method in conscious fed mice. We found that centrally administered nesfatin-1 decreased food intake and inhibited gastroduodenal motility in mice. These results suggest that nesfatin-1 influences gut motility and feeding behaviour.

Zinc as an Appetite Stimulator - The Possible Role of Zinc in the Progression of Diseases Such as Cachexia and Sarcopenia

Zinc is required by humans and animals for many physiological functions, such as growth, immune function, and reproduction. Zinc deficiency induces a number of physiological problems, including anorexia, growth retardation, dermatitis, taste disorder, and hypogonadism. Although it is clear that zinc deficiency produces specific and profound anorexia in experimental animals, the connection between zinc deficiency and anorexia is less certain. We were the first to show that orally, but not intraperitoneally, administered zinc rapidly stimulates food intake through orexigenic peptides coupled to the afferent vagus nerve using rats during early-stage zinc deficiency without decreased zinc concentrations in plasma and tissues. We confirmed that a zinc-sufficient diet containing zinc chloride acutely stimulated food intake after short-term zinc deprivation. We also found that orally administered zinc sulfate increased the expression of NPY and orexin mRNA after administration. Using vagotomized rats, we tested whether the increase in food intake after oral administration of zinc was mediated by the vagus nerve. In sham-operated rats, the oral administration of zinc stimulated food intake, whereas zinc and saline administrations did not exhibit differing effects in vagotomized rats. We conclude that zinc stimulates food intake in short-term zinc-deficient rats through the afferent vagus nerve with subsequent effects on hypothalamic peptides associated with food intake regulation. In this review, we describe recent research investigating the roles of zinc as an appetite stimulator in food intake regulation, along with research about hypothalamus, ghrelin, leptin and zinc receptor, and clinical application about anorexia nervosa, cachexia and sarcopenia. The article also presents some promising patents on zinc.

Biological effects of obestatin

Obestatin, a 23-amino-acid peptide, is derived from the preproghrelin precursor. Obestatin was identified in 2005 as a hormone regulating food intake and energy, and having opposite effects to those of ghrelin. However, as studies have progressed, many disputes on the physiological function of obestatin have emerged. The food intake suppressive effects of obestatin have not been replicated in many studies. Nonetheless, many biological roles of obestatin have been revealed, and obestatin is thought to be associated with a variety of biological functions such as feeding, drinking, incretion, memory, and sleep, and with neuropsychiatric manifestations. The biological effects of obestatin will be reviewed in this article.

Hydrogen Improves Glycemic Control in Type1 Diabetic Animal Model by Promoting Glucose Uptake into Skeletal Muscle

Hydrogen (H2) acts as a therapeutic antioxidant. However, there are few reports on H2 function in other capacities in diabetes mellitus (DM). Therefore, in this study, we investigated the role of H2 in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ)-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H2 promoted 2-[14C]-deoxy-d-glucose (2-DG) uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K), protein kinase C (PKC), and AMP-activated protein kinase (AMPK), although it did not stimulate the translocation of Glut2 in Hep G2 cells. H2 significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p.) and oral (p.o.) administration. However, long-term p.o. administration of H2 had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H2 exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.

Plasma klotho levels decrease in both anorexia nervosa and obesity.

OBJECTIVE The aim of this study was to examine the associations of klotho with body mass index (BMI) in patients with restricting-type anorexia nervosa (r-AN) and obesity. METHOD We examined plasma klotho as well as adiponectin and its isoform levels in comparison in 11 obese patients, 12 r-AN patients, and 11 control participants. RESULTS Plasma klotho levels were markedly lower in the obesity and r-AN groups than in the control group. Moreover, plasma klotho levels increased significantly after the recovery of BMI in r-AN patients. Total and high-molecular-weight adiponectin levels were significantly decreased only in obesity. There was no relationship between klotho and total adiponectin levels or klotho and respective adiponectin isoform levels in the entire study population. CONCLUSIONS These results suggest that klotho may reflect normal nutritional state, and that the decrease of klotho in r-AN and obesity may underlie the deteriorating processes of these disorders.

Stimulation of leptin secretion by insulin

Leptin has a crucial role in regulating food intake and maintaining metabolic homeostasis. Although little is known about the process of leptin secretion, insulin, which has an important role in the metabolism of glucose and lipids, is believed to regulate leptin secretion through a posttranscriptional mechanism in the short term, and via glucose metabolism in the long term. The gastric mucosa secretes leptin, but this mechanism has not been completely elucidated. Understanding the mechanism of insulin-regulated leptin secretion could lead to the development of new treatment methods for obesity and its comorbidities, which are serious public health concerns.

A case of anorexia nervosa with disseminated intravascular coagulation syndrome

A 36-year-old Japanese woman with anorexia nervosa (AN) was admitted to our department because of severe emaciation. Although we were thorough in her clinical management and were careful to avoid precipitating refeeding syndrome, disseminated intravascular coagulation (DIC) developed 3 weeks after hospitalization. We treated her for DIC with sepsis using anticoagulants, protease inhibitors, antithrombin, and platelet concentrate transfusion. To treat her bacterial infection, we administered antimicrobial drugs and immunoglobulin. We began probiotic and prebiotic (synbiotics) treatment for bacterial translocation. We think that the prevention of sepsis via bacterial translocation is an important aspect of care for patients with severe AN in addition to the prevention of refeeding syndrome.

The role of CRF family peptides in the regulation of food intake and anxiety-like behavior

Abstract Corticotropin-releasing factor (CRF) and the urocortins (UCN1, UCN2, and UCN3) belong to the CRF family of peptides and are the major regulators of the adaptive response to internal and external stresses. The actions of CRF and UCNs are mediated through two receptor subtypes: CRF receptor 1 (CRFR1) and CRFR2. Their physiological roles, among other functions, include the regulation of food intake and anxiety-like behavior. In this review, we describe the progress that has been made towards understanding how anxiety- and depression-like behavior and food intake are regulated by CRF, UCN1, UCN2, and UCN3.

Tu1880 Activation of the Hypothalamic Serotonin/Corticotropin-Releasing Factor Pathway Induces Ghrelin Insufficiency and Resistance in Cancer Cachexia Syndrome

than cN). Multivariable logistic regression analysis was done to identify independent predictors for pCR. Results: A total number of 1593 patients were included, with a median interval of 14 weeks between radiotherapy and surgery (range 6-85 weeks; interquartile range 1216 weeks). Outcome measures were calculated for intervals up to week 13 (N=312), in week 13/14 (N=511), in week 15/16 (N=406) and after week 16 (N=364). Age, tumor localization and R0 resection rate were equally distributed between the four groups; significant differences were found for cT stage (cT4 17.3%, 18.4%, 24.5%, 26.6% respectively; P= 0.010), and cM stage (cM1 4.4%, 4.8%, 8.9%, 14.9% respectively; P=0.000). Resection in week 15/16 resulted in the highest percentage of pCR (18.0%; P=0.013). Results for secondary endpoints in week 15/16 were: T downstaging 55.2% (P=0.165), N downstaging 58.6% (P=0.036) and (near) complete response 23.2% (P=0.124). Resection in week 15/16 was independently associated with pCR in a multivariable logistic regression analysis (HR 1.6; 95%CI 1.1-2.2). Conclusion: Based on differences in clinical practice regarding timing of TME surgery among 92 Dutch hospitals, we were able to demonstrate that the pCR rate after neoadjuvant CRT for rectal cancer is related to the time interval between radiotherapy and surgery. Delaying surgery until the 15th or 16th week after start of CRT seems to result in the highest chance of pCR, both in univariable and multivariable analysis. This corresponds with a time interval of approximately 10 to 11 weeks between end of CRT and surgery, based on a conventional five weeks treatment period.

1034 The Dual Action of the KAMPO MEDICINE Rikkunshito Offers a Promising New Approach for the Treatment of Ghrelin Resistance in Cancer Anorexia-Cachexia

G A A b st ra ct s using HRM. Methods: Studies were performed in 12 healthy volunteers (5 males, median age 23 years). Nausea was induced by a motion video of a rotating and tilted view of a landscape and rated on a VAS scale ranging from 1-4 (no/mild/moderate/severe nausea) every minute until complete recovery. GEP and anatomical changes were assessed with HRM. FP was measured from the five pressure channels positioned below the LES. Reflux was assessed by impedance-pH (MII-pH). After intubation, a baseline (BL) recording of 15min was obtained. This was followed by the motion video (until the volunteer perceived nausea VAS≥3 (at least 10min, max 20min)) followed by 30min recovery recording. Results correspond to measurements at peak nausea, early recovery (first 5 min after the end of the motion video) and late recovery (last 5min of the 30min recovery period). Results: 10/12 subjects showed a drop in FP during peak nausea compared to BL (-4.0±0.8mmHg; p= 0.005) with 8/10 subjects showing a partial or complete FP return during late recovery. 8/ 10 subjects who showed FP drop also showed a drop of LES pressure during peak nausea (-8.8±2.5mmHg; p=0.04) with 9/10 subjects showing a partial or complete return of LES pressure during late recovery. Peak nausea preceded peak fundus and LES relaxation. 8/10 subjects showed increase in length of the oesophageal body during peak nausea and early recovery (+0.8±0.2cm and +0.7±0.1cm; p,0.05) whereas a shortening of the oesophagus was observed during late recovery (-0.6±0.2cm; p,0.05). There was a significant decrease in LES thickness during peak nausea (-0.8±0.3cm; p,0.05). The number of swallows was comparable during BL/nausea/recovery. MII-pH showed normal acid exposure and 0-2 reflux episodes during total recording times. The number of TLESRs was significantly greater during the recovery period compared to the nausea period (p=0.01). Conclusion: Fundus and GEJ changes during nausea are different from those observed during meals, TLESRs and vomiting. Peak nausea is followed by a drop in fundus and LES pressure, oesophageal lengthening and a decrease in LES thickness. LES relaxation during nausea is incomplete and not accompanied by reflux. Whether anatomical changes provoke the sensation of nausea or vice versa is unknown, however the time sequence in our experiment suggests the latter.