neuropeptide-y and Encephalitis

Topics: Agouti-Related Protein; Animals; Cell Line; Encephalitis; Gene Expression Regulation; Hypothalamus; Inflammation Mediators; Insulin Resistance; Mice; Neurons; Neuropeptide Y; Rats; RNA, Messenger; Signal Transduction; Tumor Necrosis Factor-alpha

Diet-induced hypothalamic inflammation is an important mechanism leading to dysfunction of neurons involved in controlling body mass. Studies have shown that polyunsaturated fats can reduce hypothalamic inflammation. Here, we evaluated the presence and function of RvD2, a resolvin produced from docosahexaenoic acid, in the hypothalamus of mice.. Male Swiss mice were fed either chow or a high-fat diet. RvD2 receptor and synthetic enzymes were evaluated by real-time PCR and immunofluorescence. RvD2 was determined by mass spectrometry. Dietary and pharmacological approaches were used to modulate the RvD2 system in the hypothalamus, and metabolic phenotype consequences were determined.. All enzymes involved in the synthesis of RvD2 were detected in the hypothalamus and were modulated in response to the consumption of dietary saturated fats, leading to a reduction of hypothalamic RvD2. GPR18, the receptor for RvD2, which was detected in POMC and NPY neurons, was also modulated by dietary fats. The substitution of saturated by polyunsaturated fats in the diet resulted in increased hypothalamic RvD2, which was accompanied by reduced body mass and improved glucose tolerance. The intracerebroventricular treatment with docosahexaenoic acid resulted in increased expression of the RvD2 synthetic enzymes, increased expression of anti-inflammatory cytokines and improved metabolic phenotype. Finally, intracerebroventricular treatment with RvD2 resulted in reduced adiposity, improved glucose tolerance and increased hypothalamic expression of anti-inflammatory cytokines.. Thus, RvD2 is produced in the hypothalamus, and its receptor and synthetic enzymes are modulated by dietary fats. The improved metabolic outcomes of RvD2 make this substance an attractive approach to treat obesity.

Topics: Animals; Anti-Inflammatory Agents; Calcium-Binding Proteins; Cytokines; Diet, High-Fat; Disease Models, Animal; Docosahexaenoic Acids; Encephalitis; Gene Expression Regulation; Glucose Tolerance Test; Hypothalamus; Male; Mice; Microfilament Proteins; Neurons; Neuropeptide Y; Obesity; Oxygen Consumption; Pro-Opiomelanocortin; Receptors, G-Protein-Coupled

Obesity can be associated with systemic low-grade inflammation that contributes to obesity-related metabolic disorders. Recent studies raise the possibility that hypothalamic inflammation contributes to the pathogenesis of diet-induced obesity (DIO), while another study reported that obesity decreases the expression of pro-inflammatory cytokines in spleen. The following study examines the hypothesis that obesity suppresses the splenic synthesis of the anti-inflammatory cytokine, interleukin (IL)-10, thereby resulting in chronic hypothalamic inflammation. The results showed that due to oxidative stress or apoptosis, the synthesis of splenic IL-10 was decreased in DIO when compared with non-obesity rats. Splenectomy (SPX) accelerated DIO-induced inflammatory responses in the hypothalamus. Interestingly, SPX suppressed the DIO-induced increases in food intake and body weight and led to a hypothalamic pro-inflammatory state that was similar to that produced by DIO, indicating that hypothalamic inflammation exerts a dual effect on energy metabolism. These SPX-induced changes were inhibited by the systemic administration of IL-10. Moreover, SPX had no effect on hypothalamic inflammatory responses in IL-10-deficient mice. These data suggest that spleen-derived IL-10 plays an important role in the prevention of hypothalamic inflammation and may be a therapeutic target for the treatment of obesity and hypothalamic inflammation.

Topics: Aldehydes; alpha-MSH; Animals; Apoptosis; Area Under Curve; Body Weight; Cytokines; Diet, High-Fat; Disease Models, Animal; Eating; Encephalitis; Hypothalamus; In Situ Nick-End Labeling; Interleukin-10; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons; Neuropeptide Y; Obesity; Oxidative Stress; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Spleen; Splenectomy

The purpose of this study was to test the continuing validity of the hypothesis that neuropeptide Y (NPY) produced in the brain controls food intake through an interaction with the NPY Y(5) receptor subtype.. The hypothesis was tested using CGP 71683A a potent and highly selective non-peptide antagonist of the NPY Y(5) receptor which was administered into the right lateral ventricle of obese Zucker fa/fa rats.. Intraventricular injection of 3.4 nmol/kg NPY increased food intake during a 2 h test period. Doses of CGP 71683A in excess of 15 nmol/kg (i.cv.) resulted in blockade of the increase in food intake produced by NPY. Repeated daily injection of CGP 71683A (30--300 nmol/kg, i.cv.) immediately before the dark phase produced a dose-dependent and slowly developing decrease in food intake. CGP 71683A has a low affinity for NPY Y(1), Y(2) and Y(4) receptors but a very high affinity for the NPY Y(5) receptor (Ki, 1.4 nM). Surprisingly, CGP 71683A had similarly high affinity for muscarinic receptors (Ki, 2.7 nM) and for the serotonin uptake recognition site (Ki, 6.2 nM) in rat brain. Anatomic analysis of the brain after treatment with CGP 71683A demonstrated an inflammatory response associated with the fall in food intake.. While the fall in food intake in response to CGP 71683A may have a Y(5) component, interactions with other receptors or inflammatory mediators may also play a role. It is concluded that CGP 71683A is an imprecise tool for investigating the role of the NPY Y(5) receptor in the control of physiological processes including food intake. International Journal of Obesity (2001) 25, 84-94

Topics: Animals; Dose-Response Relationship, Drug; Eating; Encephalitis; Energy Intake; Injections, Intraventricular; Male; Naphthalenes; Neuropeptide Y; Obesity; Pyrimidines; Rats; Rats, Wistar; Rats, Zucker; Receptors, Muscarinic; Receptors, Neuropeptide Y; Receptors, Serotonin; Time Factors