Marie Amitani

Plasma nesfatin-1 concentrations in restricting-type anorexia nervosa

Restricting-type anorexia nervosa (AN-R) is characterized by chronic food restriction and severe emaciation due to various cognitive biases such as a distorted self-image. In spite of several treatments, AN-R continues to be a refractory disease because of its unknown pathogenesis. Although previous studies have shown that changes in feeding regulatory peptides such as ghrelin are involved in anorexia, few reports have described the relationship between AN-R and nesfatin-1, a recently identified satiety peptide. Therefore, we examined the plasma nesfatin-1 levels in AN-R patients to determine its role in AN-R. A total of 15 women participated in the study; 7 patients with AN-R and 8 age-matched healthy controls (average BMI, 13.02 ± 0.30 vs. 21.57 ± 0.48, respectively). Our results showed that plasma nesfatin-1 levels were significantly lower in AN-R group than in control group (6.23 ± 0.70 ng/ml vs. 8.91 ± 0.85 ng/ml, respectively, P<0.05). Plasma acyl ghrelin and des-acyl ghrelin levels were significantly higher in AN-R group than in control group (acyl ghrelin: 62.4 ± 10.15 fmol/ml vs. 27.20 ± 5.60 fmol/ml, P<0.01 and des-acyl ghrelin: 300.17 ± 55.95 fmol/ml vs. 107.34 ± 40.63 fmol/ml, P<0.05). Although AN-R is associated with emaciation for a prolonged period, our result suggested that nesfatin-1 levels may be regulated by nutrition status and response to starvation.

The role of leptin in the control of insulin-glucose axis

Obesity and diabetes mellitus are great public health concerns throughout the world because of their increasing incidence and prevalence. Leptin, the adipocyte hormone, is well known for its role in the regulation of food intake and energy expenditure. In addition to the regulation of appetite and satiety that recently has attracted much attentions, insight has also been gained into the critical role of leptin in the control of the insulin-glucose axis, peripheral glucose and insulin responsiveness. Since the discovery of leptin, leptin has been taken for its therapeutic potential to obesity and diabetes. Recently, the therapeutic effects of central leptin gene therapy have been reported in insulin-deficient diabetes in obesity animal models such as ob/ob mise, diet-induced obese mice, and insulin-deficient type 1 diabetes mice, and also in patients with inactivating mutations in the leptin gene. Herein, we review the role of leptin in regulating feeding behavior and glucose metabolism and also the therapeutic potential of leptin in obesity and diabetes mellitus.

Rosmarinic acid ameliorates hyperglycemia and insulin sensitivity in diabetic rats, potentially by modulating the expression of PEPCK and GLUT4

Background Rosmarinic acid (RA) is a natural substance that may be useful for treating diabetes mellitus. The present study investigated the effects of RA on glucose homeostasis and insulin regulation in rats with streptozocin (STZ)-induced type 1 diabetes or high-fat diet (HFD)-induced type 2 diabetes. Methods Glucose homeostasis was determined using oral glucose tolerance tests and postprandial glucose tests, and insulin activity was evaluated using insulin tolerance tests and the homeostatic model assessment for insulin resistance. Additionally, the protein expression levels of PEPCK and GLUT4 were determined using Western blot analysis. Results RA administration exerted a marked hypoglycemic effect on STZ-induced diabetic rats and enhanced glucose utilization and insulin sensitivity in HFD-fed diabetic rats. These effects of RA were dose-dependent. Meanwhile, RA administration reversed the STZ- and HFD-induced increase in PEPCK expression in the liver and the STZ- and HFD-induced decrease in GLUT4 expression in skeletal muscle. Conclusion RA reduces hyperglycemia and ameliorates insulin sensitivity by decreasing PEPCK expression and increasing GLUT4 expression.

Control of food intake and muscle wasting in cachexia

Cachexia is characterized by anorexia, weakness, weight loss, and muscle wasting. Anorexia and muscle wasting are the key features of cachexia and they affect mortality, morbidity, and quality of life. Consistent studies have found that feeding-regulating peptides such as melanocortin, ghrelin, and leptin are related to muscle metabolism, and the balance of catabolism and anabolism in muscle is regulated in the hypothalamus, which also regulates appetite and energy expenditure. In cachexia, proinflammatory cytokines, such as TNF-α, IL-1, IL-6 and Angiotensin II induce muscle atrophy. The mechanism is suggested via upregulation of MuRF1 and MAFbx. In contrast, the orexigenic peptide, AgRP and ghrelin have the effect to decrease proinflammatory cytokines and increase body weight, food intake, and muscle mass. The understandings of the pathological mechanism of anorexia and muscle metabolism in view of the crosstalk between brain and muscle will open the new way for the management of cachexia. In this review, we describe recent experimental and clinical studies that have examined the regulation of food intake and muscle wasting in cachexia. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.

The role of adiponectin multimers in anorexia nervosa

OBJECTIVE Anorexia nervosa (AN) continues to be a refractory disease because of its unknown pathogenesis. The role of adiponectin in AN has not been clarified. Moreover, few reports have described the relations between adiponectin isoforms and AN in the physical and psychological states. Therefore, we measured plasma adiponectin and its isoforms levels in patients with AN to examine their roles in AN. METHODS Eighteen women participated in this study: nine patients with AN and nine age-matched healthy controls. We examined plasma adiponectin and its isoforms levels in all subjects and administered three types of psychological test to patients with AN: the Eating Disorders Inventory-2, the Maudsley Obsessional-Compulsive Inventory, and the Beck Depression Inventory-2. RESULTS We found that the percentage of high-molecular-weight (HMW) to total adiponectin (%HMW) was significantly low and the percentage of low-molecular-weight (LMW) to total adiponectin (%LMW) was significantly high in the AN group compared with the control group. The %HMW positively and the %LMW negatively correlated with body mass index in the entire study population. The %HMW was also positively correlated with psychological symptoms such as social insecurity or cleaning evaluated with the Eating Disorders Inventory-2 or the Maudsley Obsessional-Compulsive Inventory. CONCLUSIONS Our study indicates that all adiponectin isoforms should be evaluated in patients with AN in addition to total adiponectin. The decreased %HMW and the increased %LMW that were correlated with the body mass index and some components of psychopathology in our patients may indicate a complex role of adiponectin isoforms in maintaining energy homeostasis and emotion during extreme malnourishment.

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.

One‐year intranasal application of growth hormone releasing peptide‐2 improves body weight and hypoglycemia in a severely emaciated anorexia nervosa patient

In Japan, growth hormone releasing peptide‐2 (GHRP‐2) is clinically used as a diagnostic agent for growth hormone secretion deficiency, but the therapeutic application of GHRP‐2 has not been studied in anorexia nervosa. GHRP‐2 reportedly exhibits agonistic action for ghrelin receptor and increases food intake.

Intelligence quotient and cognitive functions in severe restricting-type anorexia nervosa before and after weight gain

OBJECTIVE Restricting-type anorexia nervosa (AN-R), characterized by severe emaciation with long-term food restriction, is often difficult to treat. The present study investigated the overall intelligence quotient (IQ) scores and cognitive functions of patients with AN-R. METHODS Fourteen female inpatients with AN-R (body mass index 12.84 ± 0.41 kg/m²) and 10 healthy female participants participated in this study from 2007 through 2010. The Wechsler Adult Intelligence Scale, Third Edition and the Eating Disorder Inventory-II were administered. This research was performed at Kagoshima University Hospital. RESULTS In the AN-R group, overall IQ scores showed borderline intelligence (e.g., full-scale IQ 75.86 ± 1.79, P < 0.01); the scores were significantly lower than those in the comparison group. There were negative correlations between lower IQs and higher Eating Disorder Inventory-II scores. After the weight restoration, the IQ scores of subjects with AN-R with regard to the visuospatial scales were significantly higher than before (P < 0.01); however, the auditory cognitive scores were unchanged. CONCLUSION These lower IQ scores could be connected to the psychological and behavioral traits in patients with AN-R. These problems should be considered by medical staff members who seek to treat patients with AN-R successfully.

Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer

Oxidative stress is involved in cancer development. Hydrogen (H2) is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. This study aimed to investigate the role of H2 incombination with 5-fluorouracil (5-FU) in cancer treatment both in vitro and in vivo using the colon 26 cell line. The survival rate was determined using the Kaplan–Meier survival test, and cell viability was assessed using cell viability imaging kit and the MTT assay, and activation of the cell apoptosis pathway (Phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), Apoptosis-inducing factor (AIF) and Caspase 3) were characterized by western blots. Hydrogen water administration improved the survival of mice with colon 26-induced cancer. Furthermore, hydrogen water enhanced cell apoptosis in cancer cells, resulting in a marked increase in the expression of p-AMPK, AIF and Caspase 3 in colon 26 cells. Hydrogen water also increased the inhibitory effect of 5-FU on colon 26 cells with spect to cell survival rate and anticancer functions. Additionally, high-content hydrogen water exhibited stronger antioxidative and anticancer activity than did the natural hydrogen water. In conclusion, high-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil.