scholarly journals Loss of leptin receptor-expressing cells in the hindbrain decreases forebrain leptin sensitivity

2020 ◽  
Vol 318 (5) ◽  
pp. E806-E816
Author(s):  
Ruth B. S. Harris
Keyword(s):  
Food Intake ◽  
Leptin Receptor ◽  
Third Ventricle ◽  
Sprague Dawley ◽  
Medial Nucleus ◽  
Leptin Sensitivity ◽  
Daily Food ◽  
Sprague Dawley Rats ◽  
Integrated Response ◽  
Transcription 3

Previous studies indicate that inhibition of food intake by leptin is mediated by an integrated response to activation of hypothalamic and hindbrain receptors. This study tested whether loss of hindbrain leptin receptor signaling changed sensitivity to forebrain leptin. Injections of leptin-conjugated saporin (Lep-Sap) into the medial nucleus of the solitary tract (NTS) were used to destroy hindbrain leptin receptor-expressing neurons of male Sprague–Dawley rats. Controls were injected with saporin conjugated with a nonsense peptide (Blk-Sap). Lep-Sap had no effect on daily food intake or body weight, but expression of phosphorylated signal transducer and activator of transcription 3 (pSTAT3) in the NTS following a peripheral injection of leptin was abolished 26 days after Lep-Sap injections. To test forebrain leptin sensitivity, Lep-Sap and Blk-Sap rats received third-ventricle injections of 0, 0.05, 0.1, 0.25, or 0.5 μg leptin. Food intake was inhibited by 0.25 and 0.5 μg leptin in Blk-Sap rats, but there was no significant effect of leptin on food intake of Lep-Sap rats. There was no difference in hypothalamic pSTAT3 in unstimulated conditions, but pSTAT3 was lower in the dorsomedial region of the ventromedial nucleus of the hypothalamus (VMH) of Lep-Sap rats compared with Blk-Sap rats following a third-ventricle injection of 0.25 μg leptin. These results are consistent with previous data showing that loss of VMH leptin receptor-expressing cells prevents weight loss caused by fourth-ventricle leptin infusion and show that the integrated response between the hindbrain and forebrain is heavily dependent on leptin activity in the VMH.

Ontogeny of diet-induced obesity in selectively bred Sprague-Dawley rats

2003 ◽  
Vol 285 (3) ◽  
pp. R610-R618 ◽  
Author(s):  
Matthew R. Ricci ◽  
Barry E. Levin
Keyword(s):  
Leptin Receptor ◽  
Splice Variants ◽  
Caloric Intake ◽  
High Energy ◽  
Sprague Dawley ◽  
Low Fat Diet ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Sprague Dawley Rats ◽  
Plasma Leptin

Outbred Sprague-Dawley rats selectively bred for their propensity to develop diet-induced obesity (DIO) become heavier on low-fat diet than those bred to be diet resistant (DR) beginning at ∼5 wk of age. Here we assessed the development of metabolic and neural functions for insights into the origins of their greater weight gain. From week 5 to week 10, chow-fed DIO rats gained 15% more body weight and ate ∼14% more calories but had only slightly greater adiposity and plasma leptin than DR rats. From day 3 through week 10, DIO and DR rats had similar mRNA expression of arcuate nucleus neuropeptide Y, proopiomelanocortin, agouti-related peptide, and all splice variants of the leptin receptor (OB-R). When fed a high-energy (HE; 31% fat) diet, 7-wk-old DIO rats had a 240% increase in plasma leptin levels after only 3 days. Despite this early leptin rise, they maintained a persistent hyperphagia and became more obese than chow-fed DIO rats and DR rats fed chow or HE diet. Their failure to reduce caloric intake, despite high levels of leptin, suggests that selectively bred DIO rats might have reduced leptin sensitivity similar to that seen in the outbred DIO parent strain.

Changes in core temperature and feeding in rats by levorphanol and dextrorphan

1979 ◽  
Vol 57 (9) ◽  
pp. 1028-1032 ◽  
Author(s):  
J. A. Thornhill ◽  
M. Hirst ◽  
C. W. Gowdey
Keyword(s):  
Food Intake ◽  
Feeding Activity ◽  
Control Period ◽  
Saline Control ◽  
Sprague Dawley ◽  
Continuous Reinforcement Schedule ◽  
Continuous Reinforcement ◽  
Subcutaneous Injections ◽  
Daily Food ◽  
Sprague Dawley Rats

Male Sprague–Dawley rats received saline for 5 days before and 5 days after daily subcutaneous injections of levorphanol or dextrorphan tartrate (8 mg base/kg) for 10 days. Core temperatures, measured by telemetry, and acquisition of food pellets on a continuous reinforcement schedule were monitored simultaneously and recorded every 30 min for each rat throughout the experiment. After the first levorphanol injections signs of acute intoxication were apparent, and a mild but delayed hyperthermia was observed and food intake declined. With repeated injections of levorphanol peak hyperthermia increased and occurred with a shorter latency after administration, as did a phase of 'stimulated' feeding activity. This phase of vigorous feeding during light hours markedly disrupted the characteristic diurnal pattern of daily food intake. During withdrawal temperatures decreased, feeding became more intermittent, and signs of increased irritability were evident in the levorphanol group. Patterns during daily injections of dextrorphan, and after its withdrawal, were similar to those in the saline control period. These results indicate that the patterns of change in temperature and feeding responses to levorphanol are similar to those found earlier with heroin, codeine, and morphine, and that these changes involve stereospecific receptors.

Effects of repeated isocaloric macronutrient loads on daily food intake of rats

1984 ◽  
Vol 247 (2) ◽  
pp. R387-R392 ◽  
Author(s):  
A. Geliebter ◽  
J. T. Liang ◽  
T. B. Van Itallie
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Corn Oil ◽  
Medium Chain Triglyceride ◽  
Repeated Administration ◽  
Sprague Dawley ◽  
Water Load ◽  
Daily Food ◽  
Sprague Dawley Rats

The effects of repeated administration of different macronutrient loads on spontaneous food intake and body weight of male Sprague-Dawley rats were studied. For 6 wk, eight groups of five rats each received two daily intragastric loads, 3.5 h apart, consisting of isocaloric amounts of one of the following: albumin, sucrose, cornstarch, corn oil, a mixture of the preceding four loads, butter, medium-chain triglyceride, or a noncaloric load of water. Spontaneous intakes of rat chow were measured 3.5 and 24 h after the first daily load. All the macronutrient loads depressed subsequent 3.5-h intakes more than the water load (P less than 0.01), and protein loads depressed 3.5-h intakes the most (P less than 0.01). The macronutrient loads also depressed 24-h intakes more than water loads (P less than 0.01) but did not differ among themselves. The mixture load depressed 3.5- and 24-h food intakes by an amount comparable with the average effects of its component loads. Neither body weight nor body fat as measured by the Lee index differed among the groups after 6 wk. The results indicate that fairly accurate long-term regulation of spontaneous energy intake occurs regardless of the type of macronutrient in the load.

Effects of leptin and cholecystokinin in rats with a null mutation of the leptin receptorLepr fak

2000 ◽  
Vol 278 (6) ◽  
pp. R1518-R1523 ◽  
Author(s):  
H. F. Wildman ◽  
S. Chua ◽  
R. L. Leibel ◽  
G. P. Smith
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Autosomal Recessive ◽  
Leptin Receptor ◽  
Third Ventricle ◽  
Recessive Mutation ◽  
Zucker Rat ◽  
Daily Food ◽  
Autosomal Recessive Mutation ◽  
Fatty Zucker Rat

The Koletsky (“corpulent”) obese rat is homozygous for an autosomal recessive mutation of the leptin receptor (Lepr) that results in hyperphagia, obesity, and hyperlipidemia. Unlike the Lepr mutation that characterizes the fatty Zucker rat ( Lepr fa ), the Koletsky mutation ( Lepr fak ) is null. Because the Leprfak mutation is null, exogenous leptin should have no effect on body weight or food intake in fak/fa k rats. We confirmed that prediction: murine leptin, administered into the third ventricle for 5 consecutive days, did not affect daily food intake or body weight in fak/fa k rats but produced dose-related inhibitions of food intake and body weight in +/+ and +/fa k rats. Although fak/fa k rats did not respond to leptin, their response to CCK-8 (4 μg/kg ip) injected before 30-min test meals of 10% sucrose was not different from that of +/+ or +/fak rats. These results demonstrate that the fak/fa k rat is a good model in which to analyze the controls of food intake, energy expenditure, and energy storage in the absence of leptin effects.

scholarly journals CCK-8 and CCK-58 differ in their effects on nocturnal solid meal pattern in undisturbed rats

2012 ◽  
Vol 303 (8) ◽  
pp. R850-R860 ◽  
Author(s):  
Miriam Goebel-Stengel ◽  
Andreas Stengel ◽  
Lixin Wang ◽  
Gordon Ohning ◽  
Yvette Taché ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Molecular Forms ◽  
Reduce Food Intake ◽  
Dark Phase ◽  
Sprague Dawley ◽  
Solid Meal ◽  
Sprague Dawley Rats ◽  
And Behavior

Various molecular forms of CCK reduce food intake in rats. Although CCK-8 is the most studied form, we reported that CCK-58 is the only detectable endocrine peptide form in rats. We investigated the dark-phase rat chow intake pattern following injection of CCK-8 and CCK-58. Ad libitum-fed male Sprague-Dawley rats were intraperitoneally injected with CCK-8, CCK-58 (0.6, 1.8, and 5.2 nmol/kg), or vehicle. Food intake pattern was assessed during the dark phase using an automated weighing system that allowed continuous undisturbed monitoring of physiological eating behavior. Both CCK-8 and CCK-58 dose dependently reduced 1-h, dark-phase food intake, with an equimolar dose of 1.8 nmol being similarly effective (−49% and −44%). CCK-58 increased the latency to the first meal, whereas CCK-8 did not. The intermeal interval was reduced after CCK-8 (1.8 nmol/kg, −41%) but not after CCK-58. At this dose, CCK-8 increased the satiety ratio by 80% and CCK-58 by 160%, respectively, compared with vehicle. When behavior was assessed manually, CCK-8 reduced locomotor activity (−31%), whereas grooming behavior was increased (+59%). CCK-58 affected neither grooming nor locomotor activity. In conclusion, reduction of food intake by CCK-8 and CCK-58 is achieved by differential modulation of food intake microstructure and behavior. These data highlight the importance of studying the molecular forms of peptides that exist in vivo in tissue and circulation of the animal being studied.

Appetite suppressant activity in plasma of rats after intestinal bypass surgery

1982 ◽  
Vol 243 (1) ◽  
pp. R60-R64 ◽  
Author(s):  
R. L. Atkinson ◽  
E. L. Brent
Keyword(s):  
Food Intake ◽  
Polymorphonuclear Leukocytes ◽  
Bypass Surgery ◽  
Aversive Conditioning ◽  
Jejunoileal Bypass ◽  
Intestinal Bypass ◽  
Sprague Dawley ◽  
Appetite Suppressant ◽  
Sprague Dawley Rats ◽  
Subsequent Intake

Male Sprague-Dawley rats with a jejunoileal bypass ate 32% less in the 1st h of refeeding after an overnight fast than did sham-bypass rats. Fasted recipients injected intraperitoneally with 6-7 ml of bypass plasma also ate 32% less (P less than 0.001) during the 1st h of refeeding than did recipients of sham-bypass plasma, but subsequent intake was not significantly different. Rectal temperature, hematocrit, white blood cell count, and percent polymorphonuclear leukocytes were not different between bypass and sham-bypass rats. A test for aversive conditioning suggested that the effect of bypass plasma was not due to illness or discomfort. These data suggest that intestinal bypass produces a transferable humoral factor that suppresses food intake and that the effect is not due to illness or discomfort. If the decreased food intake in humans after intestinal bypass is due to a similar mechanism, the possibility exists that this humoral appetite-suppressant factor may be clinically useful in the treatment of morbid obesity.

scholarly journals Effect of fish paste products, fish balls ‘tsumire’, intake in Sprague–Dawley rats

2021 ◽  
Vol 10 ◽  
Author(s):  
Kazunari Kadokura ◽  
Tsuyoshi Tomita ◽  
Kohei Suruga
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Health Management ◽  
Scientific Evidence ◽  
Inorganic Phosphorus ◽  
Organ Weight ◽  
Sprague Dawley ◽  
Group I ◽  
Sprague Dawley Rats ◽  
Group Ii

Abstract The fish paste product, fish balls ‘tsumire’, is a traditional type of Japanese food made from minced fish as well as imitation crab, kamaboko and hanpen. Although tsumire is known as a high-protein and low-fat food, there is a lack of scientific evidence on its health benefits. Hence, we aimed to investigate the effects of tsumire intake on organ weight and biomarker levels in Sprague–Dawley rats for 84 d as a preliminary study. Six-week-old male Sprague–Dawley rats were divided into two groups: group I, fed normal diets, and group II, fed normal diets with 5 % dried tsumire. Throughout the administration period, we monitored their body weight and food intake; at the end of this period, we measured their organ weight and analysed their blood biochemistry. No significant differences were observed with respect to body weight, food intake, organ weight and many biochemical parameters between the two groups. It was found that inorganic phosphorus and glucose levels were higher in group II rats than in group I rats. On the other hand, sodium, calcium, amylase and cholinesterase levels were significantly lower in group II than in group I. Interestingly, we found that the levels of aspartate aminotransferase, alanine transaminase, lactate dehydrogenase and leucine aminopeptidase in group II were significantly lower than in group I, and that other liver function parameters of group II tended to be lower than in group I. In conclusion, we consider that the Japanese traditional food, ‘tsumire,’ may be effective as a functional food for human health management worldwide.

scholarly journals Increased Hypothalamic Signal Transducer and Activator of Transcription 3 Phosphorylation after Hindbrain Leptin Injection

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1509-1519 ◽  
Author(s):  
Marieke Ruiter ◽  
Patricia Duffy ◽  
Steven Simasko ◽  
Robert C. Ritter
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Fourth Ventricle ◽  
Leptin Receptor ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Solitary Tract ◽  
Stat3 Signaling ◽  
Stat3 Phosphorylation ◽  
Transcription 3

Reduction of food intake and body weight by leptin is attributed largely to its action in the hypothalamus. However, the signaling splice variant of the leptin receptor, LRb, also is expressed in the hindbrain, and leptin injections into the fourth cerebral ventricle or dorsal vagal complex are associated with reductions of feeding and body weight comparable to those induced by forebrain leptin administration. Although these observations suggest direct hindbrain action of leptin on feeding and body weight, the possibility that hindbrain leptin administration also activates the Janus kinase/signal transducer and activator of transcription 3 (STAT3) signaling in the hypothalamus has not been investigated. Confirming earlier work, we found that leptin produced comparable reductions of feeding and body weight when injected into the lateral ventricle or the fourth ventricle. We also found that lateral and fourth ventricle leptin injections produced comparable increases of STAT3 phosphorylation in both the hindbrain and the hypothalamus. Moreover, injection of 50 ng of leptin directly into the nucleus of the solitary tract also increased STAT3 phosphorylation in the hypothalamic arcuate and ventromedial nuclei. Increased hypothalamic STAT3 phosphorylation was not due to elevation of blood leptin concentrations and the pattern of STAT3 phosphorylation did not overlap distribution of the retrograde tracer, fluorogold, injected via the same cannula. Our observations indicate that even small leptin doses administered to the hindbrain can trigger leptin-related signaling in the forebrain, and raise the possibility that STAT3 phosphorylation in the hypothalamus may contribute to behavioral and metabolic changes observed after hindbrain leptin injections.

Whey protein, as exclusively nitrogen source, controls food intake and promotes glutathione antioxidant protection in Sprague-Dawley rats

2008 ◽  
Vol 1 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Samir G. Sukkar ◽  
Franca Cella ◽  
Stefania Patriarca ◽  
Anna L. Furfaro ◽  
Francesca Abate ◽  
...  
Keyword(s):  
Food Intake ◽  
Nitrogen Source ◽  
Whey Protein ◽  
Antioxidant Protection ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Regional effect of naltrexone in the nucleus of the solitary tract in blockade of NPY-induced feeding

2000 ◽  
Vol 278 (2) ◽  
pp. R499-R503 ◽  
Author(s):  
C. M. Kotz ◽  
M. J. Glass ◽  
A. S. Levine ◽  
C. J. Billington
Keyword(s):  
Cerebrospinal Fluid ◽  
Food Intake ◽  
Paraventricular Nucleus ◽  
Opioid Receptors ◽  
The Other ◽  
Solitary Tract ◽  
Sprague Dawley ◽  
Regional Effect ◽  
Sprague Dawley Rats ◽  
Artificial Cerebrospinal Fluid

Naltrexone (NLTX) in the nucleus of the solitary tract (NTS) decreases feeding induced by neuropeptide Y (NPY) in the paraventricular nucleus (PVN). We sought to determine the NTS region most sensitive to NLTX blockade of PVN NPY-induced feeding. Male Sprague-Dawley rats were fitted with two cannulas; one in the PVN and one in a hindbrain region: caudal, medial, or rostral NTS or 1 mm outside the NTS. Animals received NLTX (0, 1, 3, 10, and 30 μg in 0.3 μl) into the hindbrain region just prior to PVN NPY (0.5 μg, 0.3 μl) or artificial cerebrospinal fluid (0.3 μl). Food intake was measured at 2 h following injection. PVN NPY stimulated feeding, and NLTX in the medial NTS significantly decreased NPY-induced feeding at 2 h, whereas administration of NLTX in the other hindbrain regions did not significantly influence PVN NPY induced feeding. These data suggest that opioid receptors in the medial NTS are most responsive to feeding signals originating in the PVN after NPY stimulation.

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