scholarly journals β-Endorphin Antagonizes the Effects of α-MSH on Food Intake and Body Weight

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4246-4255 ◽  
Author(s):  
Roxanne Dutia ◽  
Kana Meece ◽  
Shveta Dighe ◽  
Andrea J. Kim ◽  
Sharon L. Wardlaw

Proopiomelanocortin (POMC) is posttranslationally processed to several peptides including α-MSH, a primary regulator of energy balance that inhibits food intake and stimulates energy expenditure. However, another POMC-derived peptide, β-endorphin (β-EP), has been shown to stimulate food intake. In this study we examined the effects of intracerebroventricular (icv) β-EP on food intake and its ability to antagonize the negative effects of α-MSH on energy balance in male rats. A single icv injection of β-EP stimulated food intake over a 2- to 6-h period during both the light and dark cycles. This effect was, however, not sustained with chronic icv β-EP infusion. In the next study, a subthreshold dose of β-EP was injected together with Nle4, d-Phe7 (NDP)-MSH after a 16-h fast, and the negative effects of NDP-MSH on refeeding and body weight gain were partially reversed. Finally, peptide interactions were studied in a chronic icv infusion model. Weight gain and food intake were significantly suppressed in the NDP-MSH group during the entire study. A subthreshold dose of β-EP antagonized these suppressive effects on food intake and weight gain for the first 3 d. However on d 4–7, β-EP no longer blocked these effects. Of note, the stimulatory effect of β-EP on feeding and its ability to antagonize MSH were specific for β-EP1–31 and were not observed with β-EP1–27. This study highlights the importance of understanding how the balance between α-MSH and β-EP is maintained and the potential role of differential POMC processing in regulating energy balance.

Author(s):  
Lauren M. Stein ◽  
Lauren E McGrath ◽  
Rinzin Lhamo ◽  
Kieran Koch-Laskowski ◽  
Samantha M. Fortin ◽  
...  

The peptide hormone amylin reduces food intake and body weight, and is an attractive candidate target for novel pharmacotherapies to treat obesity. However, the short half-life of native amylin and amylin analogs like pramlintide limits these compounds' potential utility in promoting sustained negative energy balance. Here, we evaluate the ability of the novel long-acting amylin/calcitonin receptor agonist ZP5461 to reduce feeding and body weight in rats, and also test the role of calcitonin receptors (CTRs) in the dorsal vagal complex (DVC) of the hindbrain in the energy balance effects of chronic ZP5461 administration. Acute dose-response studies indicate that systemic ZP5461 (0.5-3 nmol/kg) robustly suppresses energy intake and body weight gain in chow- and high-fat diet (HFD)-fed rats. When HFD-fed rats received chronic systemic administration of ZP5461 (1-2 nmol/kg), the compound initially produced reductions in energy intake and weight gain, but failed to produce sustained suppression of intake and body weight. Using virally-mediated knockdown of DVC CTRs, the ability of chronic systemic ZP5461 to promote early reductions in intake and body weight gain was determined to be mediated in part by activation of DVC CTRs, implicating the DVC as a central site of action for ZP5461. Future studies should address other dosing regimens of ZP5461 to determine whether an alternative dose/frequency of administration would produce more sustained body weight suppression.


2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
Author(s):  
Mariana Peduti Halah ◽  
Paula Beatriz Marangon ◽  
Jose Antunes-Rodrigues ◽  
Lucila L. K. Elias

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.


2014 ◽  
Vol 11 (1) ◽  
pp. 36 ◽  
Author(s):  
Clare L Adam ◽  
Patricia A Williams ◽  
Matthew J Dalby ◽  
Karen Garden ◽  
Lynn M Thomson ◽  
...  

1965 ◽  
Vol 43 (2) ◽  
pp. 241-249
Author(s):  
J. R. Beaton ◽  
J. F. Sangster

Young male rats were fed one of three low-protein (5% casein) diets differing in the source of carbohydrate (sucrose, equal parts sucrose and cornstarch, or cornstarch) or a 20% casein (sucrose) diet at environmental temperatures of 24 °C or 5 °C. Replacement of sucrose with starch appeared to have a small but significant effect in increasing body weight gain for 15 days (but not the next 28 days) at 24 °C and also in animals exposed to cold for 28 days after a 15-day feeding period at 24 °C. In disagreement with results reported by Andik et al., cold exposure, although significantly increasing body weight gain and food intake in rats fed the 5% casein – starch diet, did not elicit a weight gain as great as that observed in 20% casein-fed animals at either 24 °C or 5 °C. The 24-hour food intake following a 24-hour fast exceeded the intake on the day before fasting on all diets for animals maintained at 5 °C but not 24 °C. The immediate ([Formula: see text] hour) and 24-hour food intakes of rats at 5 °C exceeded those of comparable dietary groups at 24 °C. At 5 °C, the 24-hour food intake, following the fast, of rats fed the 5% casein – starch diet exceeded that of the 20% casein-fed controls.


1986 ◽  
Vol 250 (5) ◽  
pp. E518-E522 ◽  
Author(s):  
R. Racotta ◽  
L. Ramirez-Altamirano ◽  
E. Velasco-Delgado

Chronic infusions of epinephrine, norepinephrine, or vehicle were performed in adult male rats by means of subcutaneous implanted osmotic minipumps (ALZET). The calculated dose was 180 ng/min during 7-8 days. Daily food intake and body weight were measured during this period and also 7 days before and 5 days after it. During the period of infusion, norepinephrine stopped body weight gain while epinephrine-infused rats gained weight at the same rate as controls. Once the infusion period was finished, epinephrine-infused rats gained more weight than controls, while norepinephrine-infused rats just returned to the slope of weight gain of the controls. In no group did food intake change. In a second experiment, similar infusions were carried out in other rats on the same schedule; body temperature, glycemia, and serum insulin and triiodothyronine were measured. Epinephrine infusion significantly elevated glycemia and triiodothyronine, whereas norepinephrine infusion increased temperature and serum insulin. The results obtained by chronic administration of the catecholamines support the concept of a disassociation of adrenomedullary and sympathetic nervous system metabolic effects.


2019 ◽  
Vol 317 (2) ◽  
pp. E337-E349
Author(s):  
Elizabeth T. Nguyen ◽  
Sarah Berman ◽  
Joshua Streicher ◽  
Christina M. Estrada ◽  
Jody L. Caldwell ◽  
...  

Psychological stress and excess glucocorticoids are associated with metabolic and cardiovascular diseases. Glucocorticoids act primarily through mineralocorticoid (MR) and glucocorticoid receptors (GR), and compounds modulating these receptors show promise in mitigating metabolic and cardiovascular-related phenotypes. CORT118335 (GR/MR modulator) prevents high-fat diet-induced weight gain and adiposity in mice, but the ability of this compound to reverse obesity-related symptoms is unknown. Adult male rats were subcutaneously administered CORT118335 (3, 10, or 30 mg/kg) or vehicle once daily. A 5-day treatment with CORT118335 at 30 mg/kg induced weight loss in rats fed a chow diet by decreasing food intake. However, lower doses of the compound attenuated body weight gain primarily because of decreased calorific efficiency, as there were no significant differences in food intake compared with vehicle. Notably, the body weight effects of CORT118335 persisted during a 2-wk treatment hiatus, suggesting prolonged effects of the compound. To our knowledge, we are the first to demonstrate a sustained effect of combined GR/MR modulation on body weight gain. These findings suggest that CORT118335 may have long-lasting effects, likely due to GR/MR-induced transcriptional changes. Prolonged (18 days) treatment of CORT118335 (10 mg/kg) reversed body weight gain and adiposity in animals fed a high-fat diet for 13 wk. Surprisingly, this occurred despite a worsening of the lipid profile and glucose homeostasis as well as a disrupted diurnal corticosterone rhythm, suggesting GR agonistic effects in the periphery. We conclude that species and tissue-specific targeting may result in promising leads for exploiting the metabolically beneficial aspects of GR/MR modulation.


2016 ◽  
Vol 18 (9) ◽  
pp. 1869-1876 ◽  
Author(s):  
Laura E. Rupprecht ◽  
Tracy T. Smith ◽  
Eric C. Donny ◽  
Alan F. Sved

1989 ◽  
Vol 66 (4) ◽  
pp. 1970-1975 ◽  
Author(s):  
J. Arnold ◽  
R. A. Little ◽  
N. J. Rothwell

The effects of continuously administered endotoxin on 7-day energy balance were investigated in male rats. Three groups of rats were implanted with osmotic pumps; two groups received saline-filled pumps, whereas the third received endotoxin. One of the saline groups was pair fed to match the food intake of the endotoxemic rats. After 7 days, body energy and protein and fat contents of rats were determined together with the energy content of food and feces. Endotoxin infusion not only induced fever, but it also suppressed appetite and significantly decreased body weight gain. Metabolizable energy intake was reduced by approximately 20% in infected rats. Although protein and fat gains were lowest in the endotoxin group, there appeared to be a selective loss of protein when considered as percent of body weight. Percent body fat was unaltered between the groups. Energy expenditure considered in absolute (kJ) or body weight-independent (kJ/kg0.67) terms yielded similar patterns of results; expenditure (kJ) was 10 and 20% (P less than 0.05, P less than 0.01) lower in the endotoxemic and pair-fed rats, respectively, compared with controls. Hence, compared with pair-fed rats, endotoxin-infused animals had a 10% rise in their expenditure. Brown adipose tissue thermogenesis was assessed by mitochondrial binding of guanosine 5′-diphosphate, and results showed that binding was greatest in endotoxemic rats and lowest in the pair-fed animals. The present results suggest that in this endotoxemic model appetite suppression exacerbates changes in energy balance. However, the reduction in body weight gain is also dependent on a decrease in metabolic efficiency and an increase in total energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)


1977 ◽  
Vol 232 (5) ◽  
pp. E510
Author(s):  
K A Houpt ◽  
T R Houpt ◽  
W G Pond

The energy balance of suckling Yorkshire pigs 1 day to 2 wk old was challenged by: food deprivation, glucoprivation, and caloric and noncaloric gastric loads delivered by intubation. tafter 2--4 h fasts, food intake greatly increased over nonfasted control intake during a 3-h refeeding period. This response occurred both when body weight gain was used as a measure of intake for pigs nursing on the sow and when intake was measured directly in bottle-fed pigs. Glucoprivation produced by 0.5--2 U/kg insulin did not stimulate food intake although plasma glucose fell to a mean of 49 mg/100 ml (43% of control) after 1 U/kg insulin. Gastric loads of water or 3% NACl depressed intake after 3-h fast, but 0.9% NaCl did not. All the caloric gastric loads depressed intake; in order of increasing effectiveness, they were: heavy cream, protein hydrolysate, corn oil, milk, 5% glucose, and 5% lactose. The carbohydrate loads were most effective, a result which indicates that the response was not to calories alone but to some specific nutrient, possibly glucose.


1993 ◽  
Vol 70 (1) ◽  
pp. 211-219 ◽  
Author(s):  
Kathryn A. Jackson ◽  
David L Topping

Male rats were fed on either a non-purified rodent diet (JS) or cholesterol-free purified diets containing wheat bran (WB) or oat bran (OB). Some animals were allowed normal access to their faeces for coprophagy (coprophagy +), while in others coprophagy was prevented by placement of a plastic cup over the anus (coprophagy −). Direct ingestion of faeces from the anus was observed in the former groups. Food intake was unaffected by diet or coprophagy status and body weight gain was unchanged with OB − and JS − but was significantly lower with WB −. Plasma cholesterol was highest with WB and equally lower with OB and JS and was unaffected by coprophagy status. Plasma triacylglycerols were highest with OB and were unaffected by coprophagy status. Caecal digesta mass was highest with JS, intermediate with OB and lowest with WB. Digesta mass was unaffected by coprophagy status with WB and JS but was higher with OB −. Digesta moisture content was lowest with WB + but highest with WB −. Digesta volatile fatty acid (VFA) concentrations were similarly lower with OB + and OB −, but were significantly lower with JS − and WB − than in the corresponding coprophagy + group. In all groups digesta butyrate concentrations were reduced by coprophagy prevention. Pools of total VFA, acetate and butyrate in the digesta were highest with JS. Pools of total VFA in digesta were highest with JS +, OB + and OB − and lowest with WB + and WB −. The propionate pool was highest with OB −, intermediate with OB +, and equally low in all other groups. The pool of butyrate was highest with JS + and lowest with OB −. Effects of oats and wheat on plasma cholesterol in the rat do not seem to be mediated through faecal re-ingestion.


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