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Diabulimia is the intentional omission or reduction of insulin administration in a patient with insulin-dependent diabetes mellitus (IDDM) and a coexisting eating disorder in the attempt to reduce or avoid weight gain. Although the true incidence of diabulimia is unknown, it is estimated that between 20-30% of girls and up to 40% young women with IDDM have experienced diabulimia since their diagnosis of IDDM was made. Patients with diabulimia frequently present to the emergency department, therefore early recognition of the eating disorder and prompt psychiatric consultation are essential. The aim of this review article is to summarize the existing literature about diabulimia and to raise awareness amongst emergency physicians about how to identify and treat these patients. [ABSTRACT FROM AUTHOR]

Summary: Western diets, with high consumption of simple sugars and saturated fats, contribute to the rise in the prevalence of obesity. It now seems clear that high‐fat diets cause obesity, at least in part, by modifying the composition and function of the microorganisms that colonize in the gastrointestinal tract, the microbiota. The exact pathways by which intestinal microbiota contribute to obesity remain largely unknown. High‐fat diet‐induced alterations in intestinal microbiota have been suggested to increase energy extraction, intestinal permeability and systemic inflammation while decreasing the capability to generate obesity‐suppressing short‐chain fatty acids. Moreover, by increasing systemic inflammation, microglial activation and affecting vagal nerve activity, ‘obese microbiota’ indirectly influence hypothalamic gene expression and promote overeating. Because the potential of intestinal microbiota to induce obesity has been recognized, multiple ways to modify its composition and function are being investigated to provide novel preventive and therapeutic strategies against diet‐induced obesity. [ABSTRACT FROM AUTHOR]

The adipocyte-derived hormone leptin is a peripheral signal that informs the brain about the metabolic status of an organism. Although traditionally viewed as an appetite-suppressing hormone, studies in the past decade have highlighted the role of leptin in energy expenditure. Leptin has been shown to increase energy expenditure in particular through its effects on the cardiovascular system and brown adipose tissue (BAT) thermogenesis via the hypothalamus. The current review summarizes the role of leptin signaling in various hypothalamic nuclei and its effects on the sympathetic nervous system to influence blood pressure, heart rate, and BAT thermogenesis. Specifically, the role of leptin signaling on three different hypothalamic nuclei, the dorsomedial hypothalamus, the ventromedial hypothalamus, and the arcuate nucleus, is reviewed. It is known that all of these brain regions influence the sympathetic nervous system activity and thereby regulate BAT thermogenesis and the cardiovascular system. Thus the current work focuses on how leptin signaling in specific neuronal populations within these hypothalamic nuclei influences certain aspects of energy expenditure. [ABSTRACT FROM AUTHOR]

The consumption of Western diets, high in sugar and saturated fat, is a crucial contributor to the alarming incidence of obesity and its associated morbidities. These diets have been reported to induce an inflammatory response in the hypothalamus, which promotes the development of central leptin resistance and obesity. This inflammatory signalling involves dynamic changes in the expression and activity of several mediators of the innate immune system, including toll-like receptor 4, IκB kinase- β/nuclear factor- κB, c- Jun N-terminal kinase, suppressor of cytokine signalling 3 and pro-inflammatory cytokines, as well as the induction of endoplasmic reticulum stress and autophagy defect. Although the exact cellular mechanisms remain incompletely understood, recent evidence suggests that the inflammatory response is at least mediated by interactions between neurons and non-neuronal cells such as microglia and astrocytes. Current evidence of the contribution of each inflammatory mediator to leptin resistance and diet-induced obesity ( DIO), including their reciprocal interactions and cell-type-specific effects, is reviewed and integrated in a conceptual model. Based upon this model and pharmacological intervention studies, several inflammatory mediators are proposed to be promising therapeutic targets for the treatment of DIO. [ABSTRACT FROM AUTHOR]

Eating disorders, such as anorexia nervosa ( AN), bulimia nervosa ( BN) and binge eating disorders ( BED), are described as abnormal eating habits that usually involve insufficient or excessive food intake. Animal models have been developed that provide insight into certain aspects of eating disorders. Several drugs have been found efficacious in these animal models and some of them have eventually proven useful in the treatment of eating disorders. This review will cover the role of monoaminergic neurotransmitters in eating disorders and their pharmacological manipulations in animal models and humans. Dopamine, 5- HT (serotonin) and noradrenaline in hypothalamic and striatal regions regulate food intake by affecting hunger and satiety and by affecting rewarding and motivational aspects of feeding. Reduced neurotransmission by dopamine, 5- HT and noradrenaline and compensatory changes, at least in dopamine D2 and 5- HT2C/2A receptors, have been related to the pathophysiology of AN in humans and animal models. Also, in disorders and animal models of BN and BED, monoaminergic neurotransmission is down-regulated but receptor level changes are different from those seen in AN. A hypofunctional dopamine system or overactive α2-adrenoceptors may contribute to an attenuated response to (palatable) food and result in hedonic binge eating. Evidence for the efficacy of monoaminergic treatments for AN is limited, while more support exists for the treatment of BN or BED with monoaminergic drugs. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit [ABSTRACT FROM AUTHOR]

Rats on different free-choice (fc) diets for 1 week of either chow, saturated fat and liquid sugar (fc HFHS), chow and saturated fat (fc HF), or chow and liquid sugar (fc HS) have differential levels of neuropeptide Y ( NPY) m RNA in the arcuate nucleus. Because these differences were not explained by plasma leptin levels but did predict subsequent feeding behaviour, in the present study, we first examined whether leptin sensitivity could explain these differences. Second, we focused on the role of NPY on feeding behaviour, and measured NPY m RNA levels and sensitivity to NPY after 4 weeks on the different choice diets. To determine leptin sensitivity, we measured food intake after i.p. leptin or vehicle injections in male Wistar rats subjected to the fc HFHS, fc HS, fc HF or Chow diets for 7 days. Next, we measured levels of arcuate nucleus NPY m RNA with in situ hybridisation in rats subjected to the choice diets for 4 weeks. Finally, we studied NPY sensitivity in rats subjected to the fc HFHS, fc HS, fc HF or Chow diet for 4 weeks by measuring food intake after administration of NPY or vehicle in the lateral ventricle. Leptin decreased caloric intake in rats on Chow, fc HS and fc HF but not in rats on the fc HFHS diet. After 4 weeks, rats on the fc HFHS diet remained hyperphagic, whereas fc HS and fc HF rats decreased caloric intake to levels similar to rats on Chow. By contrast to 1 week, after 4 weeks, levels of NPY m RNA were not different between the diet groups. Lateral ventricle administration of NPY resulted in higher caloric intake in fc HFHS rats compared to rats on the other choice diets or rats on Chow. Our data show that consuming a combination of saturated fat and liquid sugar results in leptin resistance and increased NPY sensitivity that is associated with persistent hyperphagia. [ABSTRACT FROM AUTHOR]

The second-generation antipsychotic drug olanzapine has become a widely prescribed drug in the treatment of schizophrenia and bipolar disorder. Unfortunately, its therapeutic benefits are partly outweighed by significant weight gain and other metabolic side effects, which increase the risk for diabetes and cardiovascular disease. Because olanzapine remains superior to other antipsychotic drugs that show less weight gain liability, insight into the mechanisms responsible for olanzapine-induced weight gain is crucial if it is to be effectively addressed. Over the past few decades, several groups have investigated the effects of olanzapine on energy balance using rat models. Unfortunately, results from different studies have not always been consistent and it remains to be determined which paradigms should be used in order to model olanzapine-induced weight gain most accurately. This review summarizes the effects of olanzapine on energy balance observed in different rat models and discusses some of the factors that appear to contribute to the inconsistencies in observed effects. In addition it compares the effects reported in rats with clinical findings to determine the predictive validity of different paradigms. [ABSTRACT FROM AUTHOR]

Feeding behaviour is crucial for the survival of an organism and is regulated by different brain circuits. Among these circuits the mesolimbic dopamine (DA) system is implicated in the anticipation and motivation for food rewards. This system consists of the dopaminergic neurons in the ventral tegmental area (VTA), and their projections to different cortico-limbic structures such as the nucleus accumbens and medial prefrontal cortex. While the importance of this system in motivational drive for different rewards, including drugs of abuse, has been clearly established, its role in energy balance remains largely unexplored. Evidence suggests that peripheral hormones such as leptin and ghrelin are involved in the anticipation and motivation for food and this might be partially mediated through their effects on the VTA. Yet, it remains to be determined whether these effects are direct effects of ghrelin and leptin onto VTA DA neurons, and to what extent indirect effects through other brain areas contribute. Elucidation of the role of leptin and ghrelin signalling on VTA DA neurons in relation to disruptions of energy balance might provide important insights into the role of this neural circuit in obesity and anorexia nervosa. [ABSTRACT FROM PUBLISHER]

Objectives:The mechanisms for how saturated fat and sugar-based beverages contribute to human obesity are poorly understood. This paper describes a series of experiments developed to examine the response of hypothalamic neuropeptides to diets rich in sugar and fat, using three different diets: a high-fat high-sugar (HFHS) choice diet with access to chow, saturated fat and a 30% sugar solution; a high-fat (HF) choice diet with access to chow and saturated fat; or to a high-sugar (HS) choice diet with access to chow and a sugar solution.Method:We first studied caloric intake, body weight gain, hormonal alterations and hypothalamic neuropeptide expression when male Wistar rats were subjected to an HFHS choice, an HF choice or an HS choice diet for 1 week. Next, we studied caloric intake and body weight gain when rats were subjected to the choice diets for 5 weeks. Finally, we measured neuropeptide expression in hepatic vagotomized rats subjected to an HFHS choice, an HF choice or an HS choice diet for 1 week.Results:In rats on an HF choice diet, plasma leptin concentrations and proopiomelanocortin (POMC) mRNA increased and neuropeptide Y (NPY) mRNA decreased. Rats on an HFHS choice diet showed identical plasma leptin concentrations as rats on an HF choice diet. However, NPY mRNA increased and POMC mRNA decreased. An HS choice diet for 1 week did not alter hypothalamic neuropeptide expression or plasma leptin concentrations. As hormonal changes did not explain the differences in hypothalamic neuropeptide expression between rats on the choice diets, we addressed whether neuronal feedback signals mediated the hypothalamic neuropeptide response. The POMC mRNA response to different diets depended on an intact innervation of liver and upper intestinal tract.Conclusion:Our data suggest that the specific combination of saturated fat and a 30% sugar solution results in hyperphagia-induced obesity and alters hypothalamic neuropeptide expression, and that the response of the melanocortin system is mediated by the hepatic vagus. [ABSTRACT FROM AUTHOR]

Feeding is a physiological process, influenced by genetic factors and the environment. In recent years, many studies have been performed to unravel the involvement of genetics in both eating behavior and its pathological forms: eating disorders and obesity. In this review, we provide a condensed introduction on the neurological aspects of eating and we describe the current status of research into the genetics of eating behavior, primarily focused on specific traits such as taste, satiation, and hunger. This is followed by an overview on the genetic studies done to unravel the heritable background of obesity and eating disorders. We examine the discussion currently taking place in the field of genetics of complex disorders and phenotypes on how to perform good and powerful studies, with the use of large-scale whole-genome association studies as one of the possible solutions. In the final part of this review, we give our view on the latest developments, including endophenotype approaches and animal studies. Studies of endophenotypes of eating behavior may help to identify core traits that are genetically influenced. Such studies would yield important knowledge on the underlying biological scaffold on which diagnostic criteria for eating disorders could be based and would provide information to influence eating behavior toward healthier living. [ABSTRACT FROM AUTHOR]

Abstract The adipose hormone, leptin, not only restrains appetite, but also influences energy expenditure. One such influence is to promote sexual maturation and fertility. The neuromodulatory circuits that mediate this effect are not well known but the present study suggests that one mediator could be melanin‐concentrating hormone (MCH). We show that the long‐form receptor (Ob‐Rb) is expressed in the zona incerta of the rat and that administration of leptin (both 0.5 µg and 1.0 µg/side) into this area of ovariectomized, oestrogen‐primed rats stimulated the release of luteinizing hormone (LH) within 1 h, the effect enduring for a further 1 h. Injections of leptin into the arcuate nucleus induced a smaller, transient rise in LH while injections into the paraventricular and ventromedial nuclei were without effect. MCH neurones are present in the zona incerta and administration of this hormone into the medial preoptic area (mPOA) stimulates LH release, therefore we investigated the possibility that MCH might mediate this effect of leptin. An injection of MCH antiserum into mPOA prevented the rise in LH normally induced by leptin injected into the zona incerta. In addition, melanocortin receptor antagonists ([D‐Arg8]ACTH(4‐10) and [Ala6]ACTH(4‐10)), previously shown to inhibit the stimulatory effect of MCH on LH release, also inhibited the effect of leptin. We propose that one route by which leptin may promote reproductive activity is by enhancing MCH release from fibres within the mPOA. Speculative mechanisms for the action of MCH include the following possibilities: MCH may be acting on the specific MCH receptor which in turn interacts with a melanocortin or melanocortin‐like receptor; MCH may bind directly to one of the melanocortin receptors; or melanocortin antagonists may interact with the MCH receptor. [ABSTRACT FROM AUTHOR]

Brainfood cluster The mission of EBRA brainfood is to increase awareness of the importance of research exploring the bidirectional links between brain health and nutrition, including the mediating systems, and to use this knowledge to identify novel nutritional, neuropsychological and neuropharmacological intervention strategies. The BRAINFOOD cluster builds new bridges across research disciplines and strengthens links to relevant stakeholders across Europe, including those involved in health and food policy. It gathers experts on brain health and nutrition that by combining and integrating strengths and complimentary expertise has the volume and capacity to develop novel intervention strategies that improve brain health of European citizens, working together with public health and the food industry. BRAINFOOD is built upon an existing network that includes: 1Discovery, with expertise in human genetics, metabolomics, nutrition, the microbiome and brain health that utilizes existing data from a variety of population and disease cohorts across the lifespan and aims to propose testable hypotheses; 2 Mechanism, with expertise in animal models, metabolomics, the microbiome and neuroscience that tests hypothesis of how the microbiome and nutrients impact on performance in different behavioral domains; 3 Experimental medicine, with expertise in psychiatry, neurology and nutrition with capacity to run randomized controlled trials; 4 Implementation, with expertise in dissemination and policy making and behavior change, to ensure that EU citizens benefit from novel insights gained in the project. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is one of the most common chronic disorders in adolescencewith still highmortality rates. Knowledge on gutbrain interaction might help to develop new treatments, as severe starvation-induced changes of the microbiome in AN-patients have been demonstrated, which do not alleviate with weight gain. In our own pilot study alpha-diversity was increased in patients with AN after short-term weight recovery, while beta diversity showed clear group differences with healthy controls before and after weight gain. A reduction of taxa belonging to Enterobacteriaceae at admission and discharge and an increase in taxa belonging to Lachnospiraceae at discharge were typically found in patients with AN. The work plan of our European project comprises an observational study and two phase II RCTs with the application of omega-3-PUFA and a multistrain psychobiotic to both, humans and rodents. With the help of a well-established animal model for AN (activity-based anorexia, ABA), the effect of stool transplants from patients to rodents will be analysed. LongitudinalMRI will be conducted in rodents together with cellular and molecular brain analyses. In addition, immune response and circulating antibodies associated with the presence of certain bacterial strains and interaction with hunger and satiety hormones will be explored. We hope that by this translational research we may systematically investigate the role of an altered microbiome for the course of AN and to identify new therapeutic tools. [ABSTRACT FROM AUTHOR]