scholarly journals Antagonism of specific corticotropin-releasing factor receptor subtypes selectively modifies weight loss in restrained rats

2008 ◽  
Vol 295 (6) ◽  
pp. R1762-R1773 ◽  
Author(s):  
Christina Chotiwat ◽  
Ruth B. S. Harris
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Third Ventricle ◽  
Corticotropin Releasing Factor ◽  
Receptor Subtypes ◽  
Mild Stress ◽  
Sustained Reduction ◽  
Corticosterone Response ◽  
Poststress Period ◽  
Corticosterone Release

Rats exposed to 3 h of restraint stress on each of 3 days (RRS) lose weight on the days of RRS and gain weight at the same rate as controls after stress ends, but do not return to the weight of controls. RRS rats also show an exaggerated endocrine response to subsequent novel stressors. Studies described here tested the effects of corticotropin-releasing factor receptor (CRFR) antagonism on RRS-induced weight loss, hypophagia, and corticosterone release during mild stress in the postrestraint period. Weight loss was not prevented by either peripheral or third-ventricle administration of a CRFR1 antagonist, antalarmin, before each restraint. Antalarmin did, however, allow recovery of body weight in the poststress period. Third-ventricle administration of a CRFR2 antagonist, antisauvagine 30, had no effect in RRS rats but caused sustained weight loss in control animals. Surprisingly, third-ventricle administration of the nonselective CRFR antagonist, astressin, caused hypophagia and reversible weight loss in control rats. It had no effect in RRS rats. None of the antagonists modified the corticosterone response to RRS or to mild stress in the post-RRS period, but antalarmin suppressed corticosterone during the period of restraint in Control rats. These results suggest that CRFR1 activation is required for the initiation of events that lead to a prolonged down-regulation of body weight in RRS rats. The sustained reduction in body weight is independent of the severity of hypophagia on the days of restraint and of RRS-induced corticosterone release.

Prevention of stress-induced weight loss by third ventricle CRF receptor antagonist

1999 ◽  
Vol 276 (5) ◽  
pp. R1461-R1468 ◽  
Author(s):  
Gennady N. Smagin ◽  
Leigh Anne Howell ◽  
Stephen Redmann ◽  
Donna H. Ryan ◽  
Ruth B. S. Harris
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Receptor Antagonist ◽  
Acute Stress ◽  
Third Ventricle ◽  
Corticotropin Releasing Factor ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Sustained Reduction ◽  
Acute Responses

We previously reported that rats exposed to repeated restraint (3 h/day for 3 days) experience temporary hypophagia and a sustained reduction in body weight compared with nonrestrained controls. Studies described here determined the involvement of central corticotropin-releasing factor (CRF) receptors in the initiation of this chronic response to acute stress. In experiment 1, Sprague-Dawley rats were fitted with cannulas in the lateral ventricle and infused with 50 μg of αhCRF-(9—41) or saline immediately before restraint on each of the 3 days of restraint. The receptor antagonist inhibited hypophagia and weight loss on day 1 of restraint but not on days 2 and 3. In experiment 2, 10 μg of αhCRF-(9—41) or saline were infused into the third ventricle immediately before each restraint. The receptor antagonist totally blocked stress-induced hypophagia and weight loss. These results demonstrate that CRF receptors located in or near the hypothalamus mediate the acute responses to stress that lead to a permanent change in the hormonal or metabolic processes that determine body weight and body composition.

Differences in response to corticotropin-releasing factor after short- and long-term consumption of a high-fat diet

2007 ◽  
Vol 293 (3) ◽  
pp. R1076-R1085 ◽  
Author(s):  
Ariadne Legendre ◽  
Emilia Papakonstantinou ◽  
Marie-Claude Roy ◽  
Denis Richard ◽  
Ruth B. S. Harris
Keyword(s):  
Mrna Expression ◽  
Third Ventricle ◽  
Corticotropin Releasing Factor ◽  
Mild Stress ◽  
High Fat ◽  
Obese Rats ◽  
Response To Stress ◽  
Corticosterone Response ◽  
Short And Long Term

We previously reported an exaggerated endocrine and weight loss response to stress in rats fed a high-fat (HF) diet for 5 days. Others report blunted stress-induced anxiety in rats made obese on a HF diet. Experiments described here tested whether sensitivity to stress-related peptides was changed in obese and nonobese HF-fed rats. Third ventricle infusion of corticotropin-releasing factor (CRF) in rats made obese on HF diet (40% kcal fat) produced an exaggerated hypophagia, which is thought to be mediated by CRF2 receptors. Obese rats responded to a lower dose of CRF for a longer time than rats fed a low-fat (LF) diet (12% kcal fat). CRF-induced release of corticosterone, which is thought to be mediated by CRF1 receptors, was not exaggerated in obese HF-fed rats. In contrast, rats fed HF diet for 5 days showed the same food intake and corticosterone response to CRF as LF-fed rats. CRF mRNA expression in the paraventricular nucleus of the hypothalamus was stimulated by mild stress (ip saline injection and placement in a novel cage) in LF-fed rats but not in rats fed HF diet for 5 days because of a nonsignificant increase in expression in nonstressed HF-fed rats. In addition, nonstressed levels of urocortin (UCN) I mRNA expression in the Edinger-Westphal nucleus were significantly inhibited in HF-fed rats. These data suggest that rats that have become obese on a HF diet show a change in responsiveness to stress peptides, whereas the increased stress response in nonobese HF-fed rats may be associated with changes in basal CRF and UCN I mRNA expression.

scholarly journals Antagonism of corticotrophin-releasing factor receptors in the fourth ventricle modifies responses to mild but not restraint stress

2008 ◽  
Vol 295 (2) ◽  
pp. R404-R416 ◽  
Author(s):  
Joanna R. Miragaya ◽  
Ruth B. S. Harris
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Fourth Ventricle ◽  
Restraint Stress ◽  
Mild Stress ◽  
Corticotrophin Releasing Factor ◽  
Repeated Restraint Stress ◽  
Corticosterone Release

Repeated restraint stress (RRS; 3 h of restraint on 3 consecutive days) in rodents produces temporary hypophagia, but a long-term downregulation of body weight. The mild stress (MS) of an intraperitoneal injection of saline and housing in a novel room for 2 h also inhibits food intake and weight gain, but the effects are smaller than for RRS. Previous exposure to RRS exaggerates hypophagia, glucocorticoid release, and anxiety-type behavior caused by MS. Here we tested the involvement of brain stem corticotrophin-releasing factor receptors (CRFR) in mediating energetic and glucocorticoid responses to RRS or MS and in promoting stress hyperresponsiveness in RRS rats. Administration of 1.3 nmol αhCRF(9-41), a nonspecific CRFR antagonist, exaggerated hypophagia and weight loss in both RRS and MS rats, whereas 0.26 nmol had no effect in RRS or MS rats. In contrast, 2 nmol of the nonspecific antagonist astressin had no effect on weight loss or hypersensitivity to subsequent MS in RRS rats, but blocked weight loss and inhibition of food intake caused by MS alone. MS rats infused with 3 nmol antisauvagine-30, a CRFR2 antagonist, did not lose weight in the 48 h after MS, but 0.3 nmol did not prevent weight loss in MS rats. These data suggest that inhibition of food intake and weight loss induced by RRS or by MS involve different pathways, with hindbrain CRFR mediating the effect of MS on body weight and food intake. Hindbrain CRFR do not appear to influence stress-induced corticosterone release in RRS rats.

Enhancement of corticosterone release by repeated injections of ACTH in the dexamethasone pre-treated rat

1983 ◽  
Vol 102 (4) ◽  
pp. 583-588 ◽  
Author(s):  
Noboru Murakami ◽  
Kiyohisa Takahashi
Keyword(s):  
Body Weight ◽  
Adrenal Gland ◽  
Adrenocorticotrophic Hormone ◽  
Blood Samples ◽  
Pulsatile Secretion ◽  
The Third ◽  
Daily Variations ◽  
Corticosterone Response ◽  
Corticosterone Release ◽  
Adrenal Corticosterone

Abstract. To examine the possibility that pulsatile secretion of adrenocorticotrophic hormone (ACTH) enhances the responsiveness of the adrenal, the blood corticosterone response to repeated injections of ACTH was determined in the dexamethasone-nembutal pre-treated rat. Treatment with dexamethasone (100 μg/100 g body weight) at 13.00 h for 2 days decreased corticosterone levels and completely abolished these daily variations in both the blood and adrenal. Under these conditions, four or five successive iv injections of 0.2 or 2 mIU ACTH were given at ½ or 1 h intervals. Blood samples were taken immediately before and at frequent intervals after injection. A significant increase of blood corticosterone levels was observed 10 min after the second injection of 0.2 mIU ACTH. Further increases in blood corticosterone levels were observed after the subsequent injections. In addition, repeated injections of 2 mIU ACTH augmented the responsiveness of the adrenal to ACTH. The second or the third injections of 2 mIU ACTH produced a greater increase in adrenal corticosterone content than did the first ACTH injection. These results suggest that when ACTH acts on the adrenal gland in a pulsatile fashion, the steroidogenic response of the adrenal to ACTH increases markedly.

scholarly journals Weight loss in rats exposed to repeated acute restraint stress is independent of energy or leptin status

2002 ◽  
Vol 282 (1) ◽  
pp. R77-R88 ◽  
Author(s):  
Ruth B. S. Harris ◽  
Tiffany D. Mitchell ◽  
Jacob Simpson ◽  
Stephen M. Redmann ◽  
Bradley D. Youngblood ◽  
...  
Keyword(s):  
Weight Loss ◽  
Weight Regain ◽  
Acute Stress ◽  
Significant Weight Loss ◽  
Endocrine Response ◽  
Sustained Reduction ◽  
Response To Stress ◽  
Corticosterone Release ◽  
Chronic Change ◽  
Crf System

Acute release of corticotropin-releasing factor (CRF) during repeated restraint (3-h restraint on each of 3 days) causes temporary hypophagia but chronic suppression of body weight in rats. Here we demonstrated that a second bout of repeated restraint caused additional weight loss, but continuing restraint daily for 10 days did not increase weight loss because the rats adapted to the stress. In these two studies serum leptin, which suppresses the endocrine response to stress, was reduced in restrained rats. Peripheral infusion of leptin before and during restraint did not prevent stress-induced weight loss, although stress-induced corticosterone release was suppressed. Restrained rats were hyperthermic during restraint, but there was no evidence that fever or elevated free interleukin-6 caused the sustained reduction in weight. Restraining food-restricted rats caused a small but significant weight loss. Food-restricted rats fed ad libitum after the end of restraint showed a blunted hyperphagia and slower rate of weight regain than their controls. These results indicate that repeated acute stress induces a chronic change in weight independent of stress-induced hypophagia and may represent a change in homeostasis initiated by repeated acute activation of the central CRF system.

scholarly journals The Effect of PPARα, PPARδ, PPARγ, and PPARpan Agonists on Body Weight, Body Mass, and Serum Lipid Profiles in Diet-Induced Obese AKR/J Mice

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-13 ◽  
Author(s):  
W. Wallace Harrington ◽  
Christy S. Britt ◽  
Joan G. Wilson ◽  
Naphtali O. Milliken ◽  
Jane G. Binz ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Fatty Acid ◽  
Weight Gain ◽  
Animal Models ◽  
Food Consumption ◽  
Antidiabetic Activity ◽  
Acid Oxidation ◽  
Receptor Subtypes ◽  
Fatty Acid Transport

Activation of peroxisome proliferator-activated receptor (PPAR)α,δ, andγsubtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. PPARpan agonists which activate all three receptor subtypes have antidiabetic activity in animal models without the weight gain associated with selective PPARγagonists. Herein we report the effects of selective PPAR agonists (GW9578, a PPARαagonist, GW0742, a PPARδagonist, GW7845, a PPARγagonist), combination of PPARαandδagonists, and PPARpan (PPARα/γ/δ) activators (GW4148 or GW9135) on body weight (BW), body composition, food consumption, fatty acid oxidation, and serum chemistry of diet-induced obese AKR/J mice. PPARαor PPARδagonist treatment induced a slight decrease in fat mass (FM) while a PPARγagonist increased BW and FM commensurate with increased food consumption. The reduction in BW and food intake after cotreatment with PPARαandδagonists appeared to be synergistic. GW4148, a PPARpan agonist, induced a significant and sustained reduction in BW and FM similar to an efficacious dose of rimonabant, an antiobesity compound. GW9135, a PPARpan agonist with weak activity at PPARδ, induced weight loss initially followed by rebound weight gain reaching vehicle control levels by the end of the experiment. We conclude that PPARαand PPARδactivations are critical to effective weight loss induction. These results suggest that the PPARpan compounds may be expected to maintain the beneficial insulin sensitization effects of a PPARγagonist while either maintaining weight or producing weight loss.

Effects of corticotropin-releasing factor on food intake and brown adipose tissue thermogenesis in rats

1988 ◽  
Vol 255 (3) ◽  
pp. E255-E259 ◽  
Author(s):  
K. Arase ◽  
D. A. York ◽  
H. Shimizu ◽  
N. Shargill ◽  
G. A. Bray
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Sympathetic Activity ◽  
Third Ventricle ◽  
Corticotropin Releasing Factor ◽  
Serum Corticosterone ◽  
The Third ◽  
Brown Adipose

Corticotropin-releasing factor (CRF) has been administered into the third ventricle of rats in acute and chronic experiments. Following a single 5-micrograms injection of CRF, there was an acute reduction in food intake at 30 and 60 min that was no longer significant at 3 h. Guanosine 5'-diphosphate (GDP) binding to mitochondria from interscapular brown adipose tissue (IBAT) of 21-h deprived rats was significantly increased 30 min after the acute infusion of 5 micrograms of CRF. Serum corticosterone was elevated in both groups but was significantly higher in the group treated with CRF. Serum glucose was unchanged. During a 7-day infusion of CRF (4.8 micrograms/day) into the third ventricle, the treated animals showed a slight, but significant, decrease in food intake but a progressive decline in body weight of 53 g over 7 days. Mitochondrial GDP binding was increased in the ad libitum-fed rats chronically treated with CRF. Serum corticosterone levels, although significantly higher than controls, were lower than following acute administration of CRF. These data show that CRF can acutely reduce food intake and increase sympathetic activity and that chronically it reduces body weight and may increase sympathetic activity without any consistent decrease in food intake.

scholarly journals Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats

2012 ◽  
Vol 302 (1) ◽  
pp. E134-E144 ◽  
Author(s):  
Gregory J. Morton ◽  
Brendan S. Thatcher ◽  
Roger D. Reidelberger ◽  
Kayoko Ogimoto ◽  
Tami Wolden-Hanson ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Area Postrema ◽  
Neuronal Response ◽  
Leptin Resistance ◽  
Low Fat Diet ◽  
Sustained Reduction ◽  
Induce Weight Loss

Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky ( fa k/ fa k) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs.

How to Maintain a Healthy Body Weight

2006 ◽  
Vol 76 (4) ◽  
pp. 208-215 ◽  
Author(s):  
Astrup
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Glycemic Index ◽  
Dairy Products ◽  
Weight Control ◽  
Healthy Body Weight ◽  
Healthy Body

The epidemic of both obesity and type 2 diabetes is due to environmental factors, but the individuals developing the conditions possess a strong genetic predisposition. Observational surveys and intervention studies have shown that excess body fatness is the major environmental cause of type 2 diabetes, and that even a minor weight loss can prevent its development in high-risk subjects. Maintenance of a healthy body weight in susceptible individuals requires 45–60 minutes physical activity daily, a fat-reduced diet with plenty of fruit, vegetables, whole grain, and lean meat and dairy products, and moderate consumption of calorie containing beverages. The use of table values to predict the glycemic index of meals is of little – if any – value, and the role of a low-glycemic index diet for body weight control is controversial. The replacement of starchy carbohydrates with protein from lean meat and lean dairy products enhances satiety, and facilitate weight control. It is possible that dairy calcium also promotes weight loss, although the mechanism of action remains unclear. A weight loss of 5–10% can be induced in almost all obese patients providing treatment is offered by a professional team consisting of a physician and dieticians or nurses trained to focus on weight loss and maintenance. Whereas increasing daily physical activity and regular exercise does not significantly effect the rate of weight loss in the induction phase, it plays an important role in the weight maintenance phase due to an impact on daily energy expenditure and also to a direct enhancement of insulin sensitivity.

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