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Different involvement of leptin signaling in food intake (FI) and body temperature (BT) in pups and adults has been suggested. However, the leptin receptor (Lepr) long-form-deficient ( db ) mouse line has not been fully examined in pups. In the most available db mouse line, wild-type (WT) mice have a mutation in the dedicator of cytokinesis 7 gene, named misty , which was recently revealed to be involved in neuronal development. Therefore, we established a line of db mice without the misty mutation using natural mating. Adult (8 weeks of age) homozygous db / db mice displayed significantly higher core body weight (BW) and FI and significantly lower core BT than WT mice. However, postnatal (2 weeks of age) db / db mice displayed similar BW and milk intake and significantly lower core BT than WT mice. Correspondingly, adult and postnatal db / db mice exhibited altered mRNA levels of hypothalamic orexigenic and anorexigenic peptide in adults but not in pups. Additionally, db / db mice displayed significantly lower mRNA levels of brown adipose tissue uncoupling protein 1 at both ages. In conclusion, the db mouse line without the misty mutation clearly showed the different involvements of the Lepr long form in FI and BT in pups and adults.

The C57BL/6:Slc23a13(-/-);Gpd2(-/-) double-knockout (a.k.a., citrin/mitochondrial glycerol 3-phosphate dehydrogenase double knockout or Ctrn/mGPD-KO) mouse displays phenotypic attributes of both neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2), making it a suitable model of human citrin deficiency. In the present study, we show that when mature Ctrn/mGPD-KO mice are switched from a standard chow diet (CE-2) to a purified maintenance diet (AIN-93M), this resulted in a significant loss of body weight as a result of reduced food intake compared to littermate mGPD-KO mice. However, supplementation of the purified maintenance diet with additional protein (from 14% to 22%; and concomitant reduction or corn starch), or with specific supplementation with alanine, sodium glutamate, sodium pyruvate or medium-chain triglycerides (MCT), led to increased food intake and body weight gain near or back to that on chow diet. No such effect was observed when supplementing the diet with other sources of fat that contain long-chain fatty acids. Furthermore, when these supplements were added to a sucrose solution administered enterally to the mice, which has been shown previously to lead to elevated blood ammonia as well as altered hepatic metabolite levels in Ctrn/mGPP-KO mice, this led to metabolic correction. The elevated hepatic glycerol 3-phosphate and citrulline levels after sucrose administration were suppressed by the administration of sodium pyruvate, alanine, sodium glutamate and MCT, although the effect of MCT was relatively small. Low hepatic citrate and increased lysine levels were only found to be corrected by sodium pyruvate, while alanine and sodium glutamate both corrected hepatic glutamate and aspartate levels. Overall, these results suggest that dietary factors including increased protein content, supplementation of specific amino acids like alanine and sodium glutamate, as well as sodium pyruvate and MCT all show beneficial effects on citrin deficiency by increasing the carbohydrate tolerance of Ctrn/mGPD-KO mice, as observed through increased food intake and maintenance of body weight., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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. [ABSTRACT FROM AUTHOR]

Abstract: 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±0.70ng/ml vs. 8.91±0.85ng/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±10.15fmol/ml vs. 27.20±5.60fmol/ml, P <0.01 and des-acyl ghrelin: 300.17±55.95fmol/ml vs. 107.34±40.63fmol/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. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study was to clarify the role of a novel agonist with high selectivity and affinity for Y4 receptors in the regulation of food intake. The Y4 receptor agonist BVD-74D was administered to C57BL/6J mice that were fed with a normal or high-fat diet, and to fatty liver Shionogi (FLS)-ob/ob mice; the food intake, water intake, and body weight gain were measured in these mice. In the mice fed with a normal diet, the cumulative food intake significantly decreased at 20min and 1h after the administration of 1mg/kg of BVD-74D and at 1, 2, 4, 8, and 24h after the administration of 10mg/kg of BVD-74D. Moreover, the cumulative water intake and body weight gain significantly decreased in these mice. Among the mice that were fed with a high-fat diet, the cumulative food intake and water intake significantly decreased 1, 2, and 4h after BVD-74D (10mg/kg) administration. Furthermore, the cumulative food intake significantly decreased 2 and 4h after BVD-74D (10mg/kg) administration in the FLS-ob/ob mice. Thus, we propose that the novel Y4 receptor agonist BVD-74D has suppressive effects on food intake, water intake, and weight gain in normal mice fed with normal diets and on food intake in normal mice fed with high-fat diets and in FLS-ob/ob mice. These findings indicate that the Y4 receptor and its agonist would be promising targets for obesity. [ABSTRACT FROM AUTHOR]