Animals always seek rewards and the related neural basis has been well studied. However, what happens when animals fail to get a reward is largely unknown, although this is commonly seen in behaviors such as predation. Here, we set up a behavioral model of repeated failure in reward pursuit (RFRP) in Drosophila larvae. In this model, the larvae were repeatedly prevented from reaching attractants such as yeast and butyl acetate, before finally abandoning further attempts. After giving up, they usually showed a decreased locomotor speed and impaired performance in light avoidance and sugar preference, which were named as phenotypes of RFRP states. In larvae that had developed RFRP phenotypes, the octopamine concentration was greatly elevated, while tβh mutants devoid of octopamine were less likely to develop RFRP phenotypes, and octopamine feeding efficiently restored such defects. By down-regulating tβh in different groups of neurons and imaging neuronal activity, neurons that regulated the development of RFRP states and the behavioral exhibition of RFRP phenotypes were mapped to a small subgroup of non-glutamatergic and glutamatergic octopaminergic neurons in the central larval brain. Our results establish a model for investigating the effect of depriving an expected reward in Drosophila and provide a simplified framework for the associated neural basis.
Acetates ; pharmacology ; Animals ; Animals, Genetically Modified ; Avoidance Learning ; physiology ; Biogenic Amines ; metabolism ; Conditioning, Operant ; physiology ; Drosophila ; physiology ; Drosophila Proteins ; genetics ; metabolism ; Feeding Behavior ; drug effects ; physiology ; Instinct ; Larva ; physiology ; Locomotion ; drug effects ; genetics ; Nervous System ; cytology ; Neurons ; physiology ; Octopamine ; metabolism ; RNA Interference ; physiology ; Reward ; Statistics, Nonparametric ; Transcription Factors ; genetics ; metabolism

OBJECTIVETo investigate the effect of Modified Zhuye Shigao Decoction (MZSD) and its components on preventing radiation esophagitis of rats.

METHODSOne hundred Wistar rats were randomly divided into 5 groups, including the control group, radiation model group, MZSD group, Zhuye Shigao Decoction (ZSD) group, and added ingredients group, 20 rats in each group. The model of radiation esophagitis of rat was established by once local radiation of 40 Gy (330 Mu/min) with a high energy linear accelerator. The administration of Chinese medicine was continued for 14 days from 7 days before radiation application in the three treatment groups. On the 7th and 14th day, the serum was isolated and the levels of inflammatory cytokines tumor necrosis factor (TNF-α), interleukin 1β (IL-1β) and IL-8 were tested. The pathological slices of esophagus were obtained, and the pathological changes were observed. During the whole process, weight and food intake were recorded each day.

RESULTSOn the 7th day after radiation, the esophagus of rats in the MZSD group was almost intact, and the pathological injury score was significantly lower than that of the radiation model group, ZSD group and added ingredients group (P<0.01). Compared with the control group, the body weight and food intake of rats in the radiation model group were significantly decreased, and the levels of TNF-α, IL-1β and IL-8 were significantly increased (P<0.05 or P<0.01), while the MZSD group showed a significant increase in body weight and food intake, and a significant decrease in the levels of TNF-α, IL-1β and IL-8 compared with the radiation model group, ZSD group and added ingredients group (P <0.05 or P<0.01).

CONCLUSIONMZSD prevents the development of radiation esophagitis probably by inhibiting the generation and release of the inflammatory cytokines TNF-α, IL-1β and IL-8.

Animals ; Body Weight ; drug effects ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Esophagitis ; drug therapy ; pathology ; prevention & control ; Esophagus ; drug effects ; pathology ; Feeding Behavior ; drug effects ; Inflammation Mediators ; metabolism ; Male ; Neutrophil Infiltration ; drug effects ; Radiation Injuries ; drug therapy ; pathology ; prevention & control ; Rats, Wistar ; Time Factors

Metformin has been reported to increase the expression of the glucagon-like peptide-1 (GLP-1) receptor in pancreatic beta cells in a peroxisome proliferator-activated receptor (PPAR)-alpha-dependent manner. We investigated whether a PPARalpha agonist, fenofibrate, exhibits an additive or synergistic effect on glucose metabolism, independent of its lipid-lowering effect, when added to metformin. Non-obese diabetic Goto-Kakizaki (GK) rats were divided into four groups and treated for 28 days with metformin, fenofibrate, metformin plus fenofibrate or vehicle. The random blood glucose levels, body weights, food intake and serum lipid profiles were not significantly different among the groups. After 4 weeks, metformin, but not fenofibrate, markedly reduced the blood glucose levels during oral glucose tolerance tests, and this effect was attenuated by adding fenofibrate. Metformin increased the expression of the GLP-1 receptor in pancreatic islets, whereas fenofibrate did not. During the intraperitoneal glucose tolerance tests with the injection of a GLP-1 analog, metformin and/or fenofibrate did not alter the insulin secretory responses. In conclusion, fenofibrate did not confer any beneficial effect on glucose homeostasis but reduced metformin's glucose-lowering activity in GK rats, thus discouraging the addition of fenofibrate to metformin to improve glycemic control.
Animals ; Blood Glucose/metabolism ; Body Weight/drug effects ; Diabetes Mellitus, Experimental/*drug therapy/*metabolism ; Drug Therapy, Combination ; Feeding Behavior/drug effects ; Fenofibrate/*pharmacology/therapeutic use ; Glucagon-Like Peptide 1/agonists/metabolism ; Glucose/*metabolism ; Glucose Tolerance Test ; Homeostasis/*drug effects ; Immunohistochemistry ; Injections, Intraperitoneal ; Insulin-Secreting Cells/drug effects/metabolism/pathology ; Lipid Metabolism/drug effects ; Male ; Metformin/*pharmacology/therapeutic use ; Peptides/administration & dosage/pharmacology ; Rats ; Receptors, Glucagon/metabolism ; Venoms/administration & dosage/pharmacology

OBJECTIVETo study the anti-feeding effect of total ginsenoside of ginseng stems and leaves on Heliothis dipsacea larvae.

METHODThe natural growing condition for lavae was simulated indoors. The anti-feeding effect of total ginsenoside on Heliothis dipsacea larvae was studied by leaf disc test.

RESULTThe total ginsenoside appeared showed a significant antifeeding effect. The Heliothis dipsacea larvae fed with the leaves of soybean treated with 2.0%, 1.0% and 0.5% total ginsenoside, respectively. At 8 h, non-selective anti-feeding rate were 93.40%, 83.42% and 75.19%, and selective anti-feeding rate were 77.53% , 73.58% and 58.86%.

CONCLUSIONThe toatal ginsenoside had significant inhibition effect on Heliothis dipsacea larvae, and inhibition effect increases as the increase of concentration ginsenoside.

Animals ; Feeding Behavior ; drug effects ; Ginsenosides ; pharmacology ; Larva ; drug effects ; growth & development ; physiology ; Moths ; drug effects ; growth & development ; physiology ; Panax ; chemistry ; Plant Extracts ; pharmacology ; Plant Leaves ; chemistry ; Plant Stems ; chemistry

The current study was designed to examine the effects of intracerebroventricular injections of SHU9119 [a nonselective melanocortin receptor (McR) antagonist] and MCL0020 (a selective McR antagonist) on the serotonin-induced eating and drinking responses of broiler cockerels deprived of food for 24 h (FD24). For Experiment 1, the chickens were intracerebroventricularly injected with 2.5, 5, and 10 microg serotonin. In Experiment 2, the chickens received 2 nmol SHU9119 before being injected with 10 microg serotonin. For Experiment 3, the chickens were given 10 microg serotonin after receiving 2 nmol MCL0020, and the level of food and water intake was determined 3 h post-injection. Results of this study showed that serotonin decreased food intake but increased water intake among the FD24 broiler cockerels and that these effects occurred in a dose-dependent manner. The inhibitory effect of serotonin on food intake was significantly attenuated by pretreatment with SHU9119 and MCL0020. However, the stimulatory effect of serotonin on water intake was not altered by this pretreatment. These results suggest that serotonin hypophagia and hyperdipsia were mediated by different mechanisms in the central nervous system, and that serotonin required downstream activation of McRs to promote hypophagia but not hyperdipsia in the FD24 chickens.
Animals ; Chickens ; Dose-Response Relationship, Drug ; Drinking Behavior/*drug effects ; Feeding Behavior/*drug effects ; Food Deprivation ; Injections, Intraventricular/veterinary ; Male ; Melanocyte-Stimulating Hormones/*pharmacology ; Oligopeptides/*pharmacology ; Receptor, Melanocortin, Type 3/*antagonists & inhibitors ; Receptor, Melanocortin, Type 4/*antagonists & inhibitors ; Serotonin/pharmacology

Chronic and heavy alcohol consumption is one of the causes of heart diseases. However, the effects of ethanol on insulin sensitivity in myocardium has been unclear. To investigate the effects of ethanol on the expression of AMP-activated protein kinase (AMPK), myocyte enhancer factor 2 (MEF2) and glucose transporter 4 (GLUT4), all of which are involved in the regulation of insulin sensitivity, in the myocardium, we performed three parts of experiments in vivo and in vitro. I: Rats were injected with 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR, 0.8 mg.kg(-1)) for 2 h. II: Rats received different dose (0.5, 2.5 or 5 g.kg(-1).d(-1)) of ethanol for 22-week. III: Primary neonatal rat cardiomyocytes were isolated and treated with or without 100 mM ethanol or 1 mM AICAR for 4 h. The cardiac protein and mRNA expression of AMPKalpha subunits, MEF2 and GLUT4 were observed by western-blotting and RT-PCR, respectively. Serum TNFalpha levels were assessed by ELISA. The results showed chronic ethanol exposure induced insulin resistance. Ethanol decreased the mRNA levels of AMPKalpha1 and alpha2, the protein levels of total- and phospho-AMPKalpha in cardiomyocytes. Similarly, ethanol showed inhibitory effects on both the mRNA and protein levels of MEF2A and 2D, and GLUT4 in a dose-response-like fashion. Correlation analysis implied an association between phospho-AMPKalpha and MEF2A or MEF2D, and between the levels of MEF2 protein and GLUT4 transcription. In addition, ethanol elevated serum TNFalpha level. Taken together, chronic ethanol exposure decreases the expression of AMPKalpha and MEF2, and is associated with GLUT4 decline in rat myocardium.
AMP-Activated Protein Kinases/genetics/*metabolism ; Aminoimidazole Carboxamide/analogs & derivatives/pharmacology ; Animals ; Enzyme Activation/drug effects ; Ethanol/*administration & dosage/*pharmacology ; Feeding Behavior/*drug effects ; Gene Expression Regulation/drug effects ; Glucose Transporter Type 4/genetics/*metabolism ; Insulin/pharmacology ; Insulin Resistance ; Male ; Myocardium/*enzymology ; Myogenic Regulatory Factors/antagonists & inhibitors/genetics/*metabolism ; Protein Isoforms/antagonists & inhibitors/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Rats ; Rats, Wistar ; Ribonucleotides/pharmacology ; Time Factors ; Tumor Necrosis Factor-alpha/blood

OBJECTIVETo explore the effect of soy isoflavone on obesity in the light of hypothalamus and peripheral orexigenic gene regulation.

METHODSFifty-four female rats were randomly assigned to 6 groups: one sham-operated group (SHAM), one ovariectomized (OVX) control group, three OVX groups fed with 400 ppm (L-SI), 1200 ppm (M-SI) and 3600 ppm (H-SI) isoflavone respectively, and one OVX group receiving 0.45 ppm diethylstilbestrol (EC). All rats were allowed to take high-fat diet for 4 weeks. Some neuropeptides were measured by RT-PCR. These neuropeptides included NPY, pro-opiomelanocortin (POMC), cocaine and amphetamine regulated transcript (CART), orexin, melanin-concentrating hormone (MCH), melanin-concentrating hormone precursor (P-MCH), ghrelin, and leptin.

RESULTSCompared with the OVX control group, the body weight and food intake in the H-SI group were reduced significantly and there was a significant dose-dependent manner in the 3 isoflavone groups. The results of RT-PCR showed that the NPY level in the 3 isoflavone groups was significantly increased and the POMC/CART gene expression decreased significantly in rats' hypothalamus compared with that in the OVX control group. However, the expression of orexin, MCH and P-MCH had no change. The peripheral grelin mRNA expression was higher in the 3 isoflavone groups, while leptin gene expression in the fat was not consistent.

CONCLUSIONSThis research showed that isoflavone could prevent obesity induced by high-fat diet and ovariectomy through regulating hypothalamus and peripheral orexigenic gene expressions associated with food intake.

Animals ; Dietary Fats ; pharmacology ; Feeding Behavior ; drug effects ; physiology ; Female ; Gene Expression Regulation ; drug effects ; Hypothalamus ; Isoflavones ; chemistry ; pharmacology ; Neuropeptides ; genetics ; metabolism ; Obesity ; Ovariectomy ; RNA, Messenger ; genetics ; metabolism ; Rats ; Soybeans ; chemistry

Ghrelin, an endogenous ligand for the growth hormone secretagogue (GHS) receptor, stimulates feeding and increases body weight. The primary action site of ghrelin has been reported to be the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamic arcuate nucleus (ARC). In addition to the hypothalamus, the caudal brainstem also appears to be an important mediator for the orexigenic activity of ghrelin. However, it is not clear whether ghrelin applied directly to the caudal brainstem activates forebrain structures. The aim of this study was to determine whether recruitment of forebrain structures was required for hyperphagic responses stimulated by ghrelin delivery within the caudal brainstem. In our experiment, all rats were surgically implanted with indwelling cannulas in the dorsal vagal complex (DVC), and ghrelin (20 pmol in 0.5 μL) was delivered to the DVC. After the injection, the orexigenic response to ghrelin was recorded by Feeding and Activity Analyser, and NPY/AgRP mRNA expressions in rat hypothalamus were detected by real-time PCR. In addition, the NPY immunoreactive neurons in the ARC were assayed by immunohistochemistry. The results showed that ghrelin significantly increased cumulative food intake at 1, 2 and 3 h after ghrelin injection, maximal response occurring at 2 h after injection. NPY/AgRP mRNA levels in ARC treated with ghrelin increased significantly compared with those in control group (injected with saline). The highest levels of NPY and AgRP mRNA were detected at 2 h after injection. The total number and mean optical density of NPY-positive neurons increased in ghrelin treated rats compared with those in control group. Consistently, ghrelin's effect was most pronounced at 2 h after injection. Taken together, we conclude that the activation of NPY/AgRP neurons in the ARC is involved in the mediation of the hyperphagic response to brainstem ghrelin administration in neurologically intact rats.
Agouti-Related Protein ; genetics ; metabolism ; Animals ; Arcuate Nucleus of Hypothalamus ; metabolism ; physiology ; Brain Stem ; metabolism ; physiology ; Feeding Behavior ; drug effects ; Ghrelin ; pharmacology ; Hyperphagia ; physiopathology ; Hypothalamus ; metabolism ; physiology ; Male ; Neurons ; metabolism ; physiology ; Neuropeptide Y ; genetics ; metabolism ; Peptide Fragments ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo determine the anti-obesity effects of oolong tea on diet-induced overweight or obesity.

METHODSA total of 8 g of oolong tea a day for 6 weeks was ingested by 102 diet-induced overweight or obese subjects. The body fat level of the subjects was determined at the same time by taking body weight, height and waist measurements. The thickness of the subcutaneous fat layer was also determined on the abdomen 3 cm to the right of the navel by the ultrasonic echo method. On the other hand, effects of oolong tea ingestion on plasma triglyceride (TG) and total cholesterol (TC) were determined. Inhibitions of pancreatic lipase by oolong tea extract and catechins in vitro were also determined.

RESULTSA total of 70% of the severely obese subjects did show a decrease of more than 1 kg in body weight, including 22% who lost more than 3 kg. Similarly, 64% of the obese subjects and 66% of the overweight subjects lost more than 1 kg during the experiment, and the subcutaneous fat content decreased in 12% of the subjects. The correlation between weight loss and subcutaneous fat decrease in men (r=0.055) was obviously lower than that in women (r=0.440, P<0.01). Body weight loss was signifificantly related to the decrease of the waist size in men (r=0.730, P<0.01) and women (r=0.480, P<0.01). Also, the correlation between subcutaneous fat reduction and decreased waist size was signifificant in women (r=0.554, P<0.01), but not in men (r=0.050, P>0.05). Moreover, the plasma levels of TG and TC of the subjects with hyperlipidemia were remarkably decreased after ingesting oolong tea for 6 weeks. In vitro assays for the inhibition of pancreatic lipase by oolong tea extract and catechins suggest that the mechanism for oolong tea to prevent hyperlipidemia may be related to the regulative action of oolong tea catechins in lipoprotein activity.

CONCLUSIONSOolong tea could decrease body fat content and reduce body weight through improving lipid metabolism. Chronic consumption of oolong tea may prevent against obesity.

Adult ; Aged ; Animals ; Beverages ; Body Height ; drug effects ; Body Weight ; drug effects ; Catechin ; pharmacology ; Cholesterol ; blood ; Diet ; Feeding Behavior ; drug effects ; Female ; Humans ; Lipase ; antagonists & inhibitors ; Male ; Middle Aged ; Obesity ; blood ; drug therapy ; Overweight ; blood ; drug therapy ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Subcutaneous Fat ; drug effects ; Sus scrofa ; Tea ; metabolism ; Triglycerides ; blood ; Young Adult

OBJECTIVETo investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism.

METHODSThree groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR (0.1RYR) or 0.3% RYR (0.3RYR). Blood (0.5 mL) was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography.

RESULTSPlasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7alpha-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 3-4 folds compared with the control value.

CONCLUSIONHypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.

Animals ; Bile Acids and Salts ; secretion ; Biological Products ; pharmacology ; Blotting, Western ; Body Weight ; drug effects ; Cholesterol ; metabolism ; Cholesterol 7-alpha-Hydroxylase ; metabolism ; Cricetinae ; Dietary Supplements ; Feces ; chemistry ; Feeding Behavior ; drug effects ; Hydroxymethylglutaryl CoA Reductases ; metabolism ; Lipoproteins ; blood ; Liver ; enzymology ; Liver X Receptors ; Naphthalenes ; analysis ; Organ Size ; drug effects ; Orphan Nuclear Receptors ; metabolism ; Receptors, LDL ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; metabolism ; Weight Gain ; drug effects