scholarly journals Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure

2014 ◽  
Vol 307 (6) ◽  
pp. R737-R745 ◽  
Author(s):  
Emily E. Noble ◽  
Charles J. Billington ◽  
Catherine M. Kotz ◽  
ChuanFeng Wang
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Taste Aversion ◽  
Conditioned Taste Aversion ◽  
Negative Regulator ◽  
Hypothalamic Nucleus ◽  
Sprague Dawley ◽  
Ventromedial Hypothalamic Nucleus ◽  
Oxytocin Receptors

Central oxytocin reduces food intake and increases energy expenditure. The ventromedial hypothalamic nucleus (VMN) is associated with energy balance and contains a high density of oxytocin receptors. We hypothesized that oxytocin in the VMN is a negative regulator of energy balance acting to reduce feeding and increase energy expenditure. To test this idea, oxytocin or vehicle was injected directly into the VMN of Sprague-Dawley rats during fasted and nonfasted conditions. Energy expenditure (via indirect calorimetry) and spontaneous physical activity (SPA) were recorded simultaneously. Animals were also exposed to a conditioned taste aversion test, to determine whether oxytocin's effects on food intake were associated with malaise. When food was available during testing, oxytocin-induced elevations in energy expenditure lasted for 1 h, after which overall energy expenditure was reduced. In the absence of food during the testing period, oxytocin similarly increased energy expenditure during the first hour, but differences in 12-h energy expenditure were eliminated, implying that the differences may have been due to the thermic effects of feeding (digestion, absorption, and metabolic processing). Oxytocin acutely elevated SPA and reduced feeding at doses that did not cause a conditioned taste aversion during both the fed and fasted states. Together, these data suggest that oxytocin in the VMN promotes satiety and acutely elevates energy expenditure and SPA and implicates the VMN as a relevant site for the antiobesity effects of oxytocin.

scholarly journals Peptide YY Mediates the Satiety Effects of the Short Chain Fatty Acid – Butyrate (P08-004-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Arashdeep Singh ◽  
Prasanth Chelikani
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Sodium Butyrate ◽  
Respiratory Quotient ◽  
Peptide Yy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Receptor Blockade ◽  
Sprague Dawley

Abstract Objectives Fermentation of fiber in the gut generates short-chain fatty acids (SCFA), such as butyrate, which decrease food intake and promote weight loss in rodent models. SCFA have been shown to enhance secretion of the gut satiety hormone peptide YY (PYY). However, it is unknown whether PYY is causative to SCFA-induced changes in energy balance. Our Objectives were to determine the dose-response effects of butyrate on energy balance, and assess whether PYY signaling is essential for mediating the satiety effects of butyrate. Methods Male Sprague Dawley rats (8 wks old, n = 39) were randomized to one of three isocaloric (4.63 kcal/g) diets: 1) control (0% sodium butyrate, n = 14), 2) 5% sodium butyrate (n = 13), or 3) 10% sodium butyrate (n = 12), and followed for upto 4 weeks. A PYY Y-2 receptor antagonist (BIIE0246) or vehicle were administered IP acutely during the study. Measurements included food intake, respiratory quotient, and energy expenditure (CLAMS®), and body composition (Minispec LF110 NMR). Results Compared to control, 10% sodium butyrate decreased food intake and respiratory quotient for 4 days, whereas, 5% sodium butyrate was ineffective. Notably, compared to control, 10% sodium butyrate decreased body weight and fat gain without changing energy expenditure. Importantly, systemic Y-2 receptor blockade stimulated food intake and increased respiratory quotient, without altering energy expenditure, only in 10% sodium butyrate group. Conclusions We found that dietary butyrate dose-dependently decreases food intake and respiratory quotient. Importantly, Y-2 receptor blockade attenuated butyrate-induced hypophagia, which supports a role for endogenous PYY in the satiety effects of dietary butyrate. Funding Sources NSERC, Heart and Stroke Foundation of Canada.  

scholarly journals Gfral-expressing Neurons Suppress Food Intake via Aversive Pathways

2020 ◽  
Author(s):  
Paul V. Sabatini ◽  
Henriette Frikke-Schmidt ◽  
Joe Arthurs ◽  
Desiree Gordian ◽  
Anita Patel ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Taste Aversion ◽  
Conditioned Taste Aversion ◽  
Mechanisms Of Action ◽  
Parabrachial Nucleus ◽  
Gastric Physiology ◽  
Anorexigenic Peptide ◽  
Artificial Activation ◽  
Meal Ingestion

AbstractTo determine the function and mechanisms of action for hindbrain neurons that express GFRAL, the receptor for the anorexigenic peptide, GDF-15, we generated Gfralcre and conditional GfralCreERT mice. While signals of infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons, the artificial activation of GfralCre- expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). Additionally, activation of the smaller population of GFRAL neurons captured by the GfralCreERT allele decreased gastric emptying and produced a CTA without suppressing food intake, suggesting that GFRAL neurons primarily modulate gastric physiology and stimulate aversive responses. GFRAL neurons most strongly innervated the parabrachial nucleus (PBN), where they targeted CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBN neurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated, pathophysiologic signals to the aversive suppression of nutrient uptake and absorption.

scholarly journals Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Irene Cimino ◽  
Debra Rimmington ◽  
Y. C. Loraine Tung ◽  
Katherine Lawler ◽  
Pierre Larraufie ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Positive Energy ◽  
Chow Diet ◽  
Chromatin Regulator ◽  
Positive Energy Balance ◽  
The Impact ◽  
Deficient Mice

AbstractNeuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat+/−p mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat+/−p mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry system, food intake in Nnat+/−p mice was hypervariable, with some mice consuming more than twice the intake seen in wild type littermates. A hyperphagic response was also seen in Nnat+/−p mice in a second, non-home cage environment. An expected correlation between body weight and energy expenditure was seen, but corrections for the effects of positive energy balance and body weight greatly diminished the effect of neuronatin deficiency on energy expenditure. Male and female Nnat+/−p mice displayed subtle distinctions in the degree of variance body weight phenotype and food intake and further sexual dimorphism was reflected in different patterns of hypothalamic gene expression in Nnat+/−p mice. Loss of the imprinted gene Nnat is associated with a highly variable food intake, with the impact of this phenotype varying between genetically identical individuals.

scholarly journals Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria

2012 ◽  
Vol 302 (7) ◽  
pp. E885-E895 ◽  
Author(s):  
Patrick Solverson ◽  
Sangita G. Murali ◽  
Adam S. Brinkman ◽  
David W. Nelson ◽  
Murray K. Clayton ◽  
...  
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Lean Mass ◽  
Metabolic Stress ◽  
Casein Diet ◽  
Wild Type ◽  
Total Fat ◽  
Spleen Mass ◽  
Main Effects

Phenylketonuria (PKU) is caused by a mutation in the phenylalanine (phe) hydroxylase gene and requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to AA formula. Our objective was to compare growth, body composition, and energy balance in Pahenu2 (PKU) and wild-type mice fed low-phe GMP, low-phe AA, or high-phe casein diets from 3–23 wk of age. The 2 × 2 × 3 design included main effects of genotype, sex, and diet. Fat and lean mass were assessed by dual-energy X-ray absorptiometry, and acute energy balance was assessed by indirect calorimetry. PKU mice showed growth and lean mass similar to wild-type littermates fed the GMP or AA diets; however, they exhibited a 3–15% increase in energy expenditure, as reflected in oxygen consumption, and a 3–30% increase in food intake. The GMP diet significantly reduced energy expenditure, food intake, and plasma phe concentration in PKU mice compared with the casein diet. The high-phe casein diet or the low-phe AA diet induced metabolic stress in PKU mice, as reflected in increased energy expenditure and intake of food and water, increased renal and spleen mass, and elevated plasma cytokine concentrations consistent with systemic inflammation. The low-phe GMP diet significantly attenuated these adverse effects. Moreover, total fat mass, %body fat, and the respiratory exchange ratio (CO2 produced/O2 consumed) were significantly lower in PKU mice fed GMP compared with AA diets. In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice.

Use of doubly labeled water technique in soldiers training for jungle warfare

1989 ◽  
Vol 67 (1) ◽  
pp. 14-18 ◽  
Author(s):  
C. H. Forbes-Ewan ◽  
B. L. Morrissey ◽  
G. C. Gregg ◽  
D. R. Waters
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Daily Intake ◽  
Doubly Labeled Water ◽  
Daily Energy Expenditure ◽  
Balance Study ◽  
Wide Range ◽  
Daily Energy ◽  
Doubly Labeled Water Method

The doubly labeled water method was used to estimate the energy expended by four members of an Australian Army platoon (34 soldiers) engaged in training for jungle warfare. Each subject received an oral isotope dose sufficient to raise isotope levels by 200–250 (18O) and 100–120 ppm (2H). The experimental period was 7 days. Concurrently, a factorial estimate of the energy expenditure of the platoon was conducted. Also, a food intake-energy balance study was conducted for the platoon. Mean daily energy expenditure by the doubly labeled water method was 4,750 kcal (range 4,152–5,394 kcal). The factorial estimate of mean daily energy expenditure was 4,535 kcal. Because of inherent inaccuracies in the food intake-energy balance technique, we were able to conclude only that energy expenditure, as measured by this method, was greater than the estimated mean daily intake of 4,040 kcal. The doubly labeled water technique was well tolerated, is noninvasive, and appears to be suitable in a wide range of field applications.

Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents

2003 ◽  
Vol 79 (4-5) ◽  
pp. 761-766 ◽  
Author(s):  
S BENOIT ◽  
E AIR ◽  
K WILMER ◽  
P MESSERSCHMIDT ◽  
K HODGE ◽  
...  
Keyword(s):  
Food Intake ◽  
Taste Aversion ◽  
Conditioned Taste Aversion ◽  
Simultaneous Assessment

scholarly journals The role of RFamide peptides in feeding

2007 ◽  
Vol 192 (1) ◽  
pp. 3-15 ◽  
Author(s):  
David A Bechtold ◽  
Simon M Luckman
Keyword(s):  
Biological Activity ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Feeding Behaviour ◽  
Animal Kingdom ◽  
Primary Function

In the three decades since FMRFamide was isolated from the clam Macrocallista nimbosa, the list of RFamide peptides has been steadily growing. These peptides occur widely across the animal kingdom, including five groups of RFamide peptides identified in mammals. Although there is tremendous diversity in structure and biological activity in the RFamides, the involvement of these peptides in the regulation of energy balance and feeding behaviour appears consistently through evolution. Even so, questions remain as to whether feeding-related actions represent a primary function of the RFamides, especially within mammals. However, as we will discuss here, the study of RFamide function is rapidly expanding and with it so is our understanding of how these peptides can influence food intake directly as well as related aspects of feeding behaviour and energy expenditure.

scholarly journals Long-term effects of ghrelin and ghrelin receptor agonists on energy balance in rats

2008 ◽  
Vol 295 (1) ◽  
pp. E78-E84 ◽  
Author(s):  
Sabine Strassburg ◽  
Stefan D. Anker ◽  
Tamara R. Castaneda ◽  
Lukas Burget ◽  
Diego Perez-Tilve ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Therapeutic Potential ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Positive Energy ◽  
High Dose ◽  
Growth Hormone Secretagogue

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is the only circulating agent to powerfully promote a positive energy balance. Such action is mediated predominantly by central nervous system pathways controlling food intake, energy expenditure, and nutrient partitioning. The ghrelin pathway may therefore offer therapeutic potential for the treatment of catabolic states. However, the potency of the endogenous hormone ghrelin is limited due to a short half-life and the fragility of its bioactivity ensuring acylation at serine 3. Therefore, we tested the metabolic effects of two recently generated GHS-R agonists, BIM-28125 and BIM-28131, compared with ghrelin. All agents were administered continuously for 1 mo in doses of 50 and 500 nmol·kg−1·day−1 using implanted subcutaneous minipumps in rats. High-dose treatment with single agonists or ghrelin increased body weight gain by promoting fat mass, whereas BIM-28131 was the only one also increasing lean mass significantly. Food intake increased during treatment with BIM-28131 or ghrelin, whereas no effects on energy expenditure were detected. With the lower dose, only BIM-28131 had a significant effect on body weight. This also held true when the compound was administered by subcutaneous injection three times/day. No symptoms or signs of undesired effects were observed in any of the studies or treated groups. These results characterize BIM-28131 as a promising GHS-R agonist with an attractive action profile for the treatment of catabolic disease states such as cachexia.

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