The effect of dietary intervention on the metabolic and behavioural impairments generated by short term high fat feeding in the rat

AbstractPrevious studies have shown that rats fed a high calorie diet rich in saturated fat for 12weeks exhibit peripheral insulin resistance and impairments of behavioural flexibility when switched from an operant delayed matching to place (DMTP) schedule to a delayed non-matching to place (DNMTP) schedule. However, the metabolic changes evoked by feeding a high fat (HF) diet can be observed within two weeks of commencing the diet. The current study has confirmed that 4weeks exposure to an HF diet resulted in increased body weight, peripheral insulin resistance and plasma leptin. Studies performed during weeks 3 and 4 on the HF diet revealed suppressed lever pressing rates and impaired behavioural flexibility in the operant DMTP/DNMTP task. When animals fed the HF diet were then returned to a standard chow (SC) diet for 5weeks their weight and blood biochemistry no longer differed from those measured in animals that had never been exposed to the HF diet. The animals restored to the SC diet exhibited a clear ability to acquire the DNMTP schedule of reinforcement although these animals continued to lever press at a lower rate when compared with animals that received the SC diet throughout. The data suggest that exposure to an HF diet diminishes the motivation to respond for a reward and, thus, the capacity to adapt behavioural performance. This deficit was ameliorated, but not totally reversed, by the dietary intervention. If also true for humans, the results suggest that deficits in behavioural flexibility develop after only a short period on a high calorie diet but may be largely reversible through simple dietary intervention, at least in the early stages of deficit development. However, the putative effects of short-term exposure to an HF diet on behavioural motivation may persist for some time after switching to a healthier low fat diet and remain a problem for those seeking to adopt a healthier diet

Regulation of Memory Function by Feeding-Relevant Biological Systems: Following the Breadcrumbs to the Hippocampus

The hippocampus (HPC) controls fundamental learning and memory processes, including memory for visuospatial navigation (spatial memory) and flexible memory for facts and autobiographical events (declarative memory). Emerging evidence reveals that hippocampal-dependent memory function is regulated by various peripheral biological systems that are traditionally known for their roles in appetite and body weight regulation. Here, we argue that these effects are consistent with a framework that it is evolutionarily advantageous to encode and recall critical features surrounding feeding behavior, including the spatial location of a food source, social factors, post-absorptive processing, and other episodic elements of a meal. We review evidence that gut-to-brain communication from the vagus nerve and from feeding-relevant endocrine systems, including ghrelin, insulin, leptin, and glucagon-like peptide-1 (GLP-1), promote hippocampal-dependent spatial and declarative memory via neurotrophic and neurogenic mechanisms. The collective literature reviewed herein supports a model in which various stages of feeding behavior and hippocampal-dependent memory function are closely linked

Astrocytes regulate GLP-1 receptor-mediated effects on energy balance

© 2016 the authors. Astrocytes are well established modulators of extracellular glutamate, but their direct influence on energy balance-relevant behaviors is largely understudied. As the anorectic effects of glucagon-like peptide-1 receptor (GLP-1R) agonists are partly mediated by central modulation of glutamatergic signaling, we tested the hypothesis that astrocytic GLP-1R signaling regulates energy balance in rats. Central or peripheral administration of a fluorophore-labeled GLP-1R agonist, exendin-4, localizes within astrocytes and neurons in the nucleus tractus solitarius (NTS), a hindbrain nucleus critical for energy balance control. This effect is mediated by GLP-1R, as the uptake of systemically administered fluorophore-tagged exendin-4 was blocked by central pretreatment with the competitive GLP-1R antagonist exendin-(9–39). Ex vivo analyses show prolonged exendin-4-induced activation (live cell calcium signaling) of NTS astrocytes and neurons; these effects are also attenuated by exendin-(9–39), indicating mediation by the GLP-1R. In vitro analyses show that the application of GLP-1R agonists increases cAMP levels in astrocytes. Immunohistochemical analyses reveal that endogenous GLP-1 axons form close synaptic apposition with NTS astrocytes. Finally, pharmacological inhibition of NTS astrocytes attenuates the anorectic and body weight-suppressive effects of intra-NTS GLP-1R activation. Collectively, data demonstrate a role for NTS astrocytic GLP-1R signaling in energy balance control

A novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference

BACKGROUND AND PURPOSE: Obesity and associated co‐morbidities, such as type 2 diabetes and non‐alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co‐morbidities. EXPERIMENTAL APPROACH: The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP‐089, on body weight, glucose homeostasis and fatty acid accumulation in liver and muscle tissue and on food preference was investigated. Furthermore, we elucidated weight‐independent effects of KBP‐089 using a weight‐matched group. KEY RESULTS: Rats fed a high‐fat diet were treated, s.c., with KBP‐089 0.625, 1.25, 2.5 μg·kg(−1) or vehicle. KB‐089 induced in a dose‐dependent and sustained weight loss (~17% by 2.5 μg·kg(−1)). Moreover, KBP‐089 reduced fat depot size and reduced lipid accumulation in muscle and liver. In Zucker Diabetic Fatty rats, KBP‐089 improved glucose homeostasis through improved insulin action. To obtain a weight‐matched group, significantly less food was offered (9% less than in the KBP‐089 group). Weight matching led to improved glucose homeostasis by reducing plasma insulin; however, these effect were inferior compared to those of KBP‐089. In the food preference test, rats fed a normal diet obtained 74% of their calories from chocolate. KBP‐089 reduced total caloric intake and induced a relative increase in chow consumption while drastically reducing chocolate consumption compared with vehicle. CONCLUSIONS AND IMPLICATIONS: The novel DACRA, KBP‐089, induces a sustained weight loss, leading to improved metabolic parameters including food preference, and these are beyond those observed simply by diet‐induced weight loss

Intersection between metabolic dysfunction, high fat diet consumption, and brain aging

Deleterious neurochemical, structural, and behavioral alterations are a seemingly unavoidable aspect of brain aging. However, the basis for these alterations, as well as the basis for the tremendous variability in regards to the degree to which these aspects are altered in aging individuals, remains to be elucidated. An increasing number of individuals regularly consume a diet high in fat, with high‐fat diet consumption known to be sufficient to promote metabolic dysfunction, although the links between high‐fat diet consumption and aging are only now beginning to be elucidated. In this review we discuss the potential role for age‐related metabolic disturbances serving as an important basis for deleterious perturbations in the aging brain. These data not only have important implications for understanding the basis of brain aging, but also may be important to the development of therapeutic interventions which promote successful brain aging.Fil: Uranga, Romina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Bruce Keller, Annadora J.. State University of Louisiana; Estados UnidosFil: Morrison, Christopher D.. State University of Louisiana; Estados UnidosFil: Fernandez Kim, Sun Ok. State University of Louisiana; Estados UnidosFil: Ebenezer, Philip J.. State University of Louisiana; Estados UnidosFil: Zhang, Le. State University of Louisiana; Estados UnidosFil: Dasuri, Kalavathi. State University of Louisiana; Estados UnidosFil: Keller, Jeffrey N.. State University of Louisiana; Estados Unido

The Behavioral and Physiological Effects of High-fat Diet and Alcohol Consumption: Sex Differences in C57BL6/J Mice

Background and Objective: Animal studies can be a great tool to investigate sex differences in a variety of different ways, including behavioral and physiological responses to drug treatments and different “lifestyle variables” such as diets. Consumption of both high-fat diets and alcohol is known to affect anxiety behaviors and overall health. This project investigated how high-fat diet and alcohol access and its combination affected the behavior and physiology of male and female C57BL/6J mice. Method: Mice were separated into three food groups: high-fat diet, 10% fat diet, and regular chow, and each group was paired with either water or 10% alcohol. Behavioral assays included diet and alcohol preference, light-dark box, open field, and feeding and drinking measurements. Physiological measures included glucose tolerance tests and measurement of brain-derived neurotrophic factor, insulin, and leptin levels. Results: Females and males differed in the open field, as male mice decreased activity, while females increased activity when consuming high-fat diet. While females consumed more ethanol than males, alcohol consumption was able to improve glucose tolerance and increase anxiety in both sexes. Lastly, females were more resistant to the physiological changes caused by high-fat diet than males, as females consuming high-fat diet exhibited decreased insulin secretion, less change to brain-derived neurotrophic factor levels, and better glucose tolerance than males consuming high-fat diet. Conclusion: These results suggest that the response to high-fat diet and alcohol consumption is sex dependent and that males are more affected both behaviorally and physiologically by high-fat diet compared to females

The impact of cafeteria diet feeding on physiology and anxiety-related behaviour in male and female Sprague-Dawley rats of different ages

There is emerging experimental evidence that hyper-energetic diets not only cause obesity but also impact on behaviour in rodents. A hyper-energetic comfort diet/cafeteria diet (CD) fed during early development programmes anxiety-related behaviour in adult age, but little is known how an obesogenic CD impacts on behaviour when fed at a later age. To this end we fed CD to Sprague-Dawley rats of both sexes at either 6 weeks or 12 months old, for a period of 6 weeks. Anxiety-related behaviour was assessed in the elevated plus maze (EPM) and the open field (OF). A glucose tolerance test was performed and metabolic indices, body weight and fat were measured. CD-fed young adult females, but not males, had a higher energy intake, due to an overconsumption of carbohydrates and fats. Only in adult CD-fed rats of both sexes did this overconsumption led to increased weight gain. Protein intake was reduced in all CD groups. Fat mass (subcutaneous, perirenal, gonadal) increased in most CD groups, whereas brown fat increased only in adults. Triacyglycerol, free fatty acid and total cholesterol concentrations increased predominantly in adult CD-fed rats. Glucose tolerance was only impaired in adult males. CD-fed adult males showed fewer entries into the aversive open arms and groomed more on the EPM, whereas adult females spent more time on these arms. In the OF, CD-fed females of both ages visited the inner zone more frequently and travelled a longer distance. The behavioural data suggests anxiolysis in CD-fed females and signs of increased anxiety in adult males. In conclusion, this study demonstrates that feeding CD leads to both obesity and behavioural changes in rats. Overall, these effects were more pronounced in older rats, with the behavioural effects being particularly gender dependent

Pre- and postnatal high fat feeding differentially affects the structure and integrity of the neurovascular unit of 16-month old male and female mice

Compelling experimental and clinical evidence supports a role for maternal obesity in offspring health. Adult children of obese mothers are at greater risk of obesity, diabetes, coronary heart disease and stroke. These offspring may also be at greater risk of age-related neurodegenerative diseases for which mid-life obesity is a risk factor. Rodent diet-induced obesity models have shown that high fat (HF) diet consumption damages the integrity of the blood-brain barrier (BBB) in the adult brain. However, there is currently little information about the effect of chronic HF feeding on the BBB of aged animals. Moreover, the long-term consequences of maternal obesity on the cerebrovasculature of aged offspring are not known. This study determined the impact of pre- and postnatal HF diet on the structure and integrity of cerebral blood vessels in aged male and female mice. Female C57Bl/6 mice were fed either a 10% fat control (C) or 45% HF diet before mating and during gestation and lactation. At weaning, male and female offspring were fed the C or HF diet until sacrifice at 16-months of age. Both dams and offspring fed the HF diet weighed significantly more than mice fed the C diet. Postnatal HF diet exposure increased hippocampal BBB leakiness in female offspring, in association with loss of astrocyte endfoot coverage of arteries. Markers of tight junctions, pericytes or smooth muscle cells were not altered by pre- or postnatal HF diet. Male offspring born to HF-fed mothers showed decreased parenchymal GFAP expression compared to offspring of mothers fed C diet, while microglial and macrophage markers were higher in the same female diet group. In addition, female offspring exposed to the HF diet for their entire lifespan showed more significant changes in vessel structure, BBB permeability and inflammation compared to male animals. These results suggest that the long-term impact of prenatal HF diet on the integrity of cerebral blood vessels differs between male and female offspring depending on the postnatal diet. This may have implications for the prevention and management of age- and obesity-related cerebrovascular diseases that differentially affect men and women

Методология синтеза архитектуры программно-технического комплекса автоматизированной системы мониторинга обстановки

Предложен подход к проектированию архитектуры программно-технического комплекса автоматизированной системы мониторинга обстановки в реальном времени, основанный на классификации решаемых функциональных задач на основе методов кластерного анализа и выбранного множества признаков подобия. Разработанный подход позволяет из множества функций системы выделить подобные (по определенным признакам) и объединить их в архитектурные компоненты (унифицированные функциональные модули).Запропоновано підхід до проектування архітектури центру обробки інформації автоматизованої системи моніторингу середовища в реальному часі, що заснований на класифікації функціональних задач на підставі методів кластерного аналізу і обраної множини ознак схожості. Розроблений підхід дозволяє вибрати із множини функцій системи схожі (за певними ознаками) і поєднати їх в архітектурні компоненти (уніфіковані функціональні модулі).The approach to designing architecture of the information processing complex of the automated real time conditions monitoring system based on classification of functional tasks on the basis of methods of cluster analysis and the chosen set of similarity attributes is offered. The developed approach allows to allocate from a set of functions the systems similar (on certain attributes) and to unite them in architectural components (unified functional modules)