Abstract P249: ICV Infusion Of AgRP Modulates Feeding Behavior And Energy Expenditure In Mice

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Vanessa Oliveira ◽  
Kirthikaa Balapattabi ◽  
John J Reho ◽  
Sebastiao D Silva ◽  
Chetan N Patil ◽  
...  

A subset of Agouti-related protein (AgRP) neurons within the arcuate nucleus express angiotensin type 1a receptors (AT1A), and genetic ablation of AT1A in these cells disinhibits AgRP gene expression and attenuates energy expenditure (EE) in mice. To further understand the role of AgRP in metabolic control, and to establish relevant dosing schedules in this species, here we tested the effect of intracerebroventricular infusion (icv) of recombinant AgRP on metabolic functions in C57BL/6J male mice. First, we examined the effects of AgRP(82-132) (21 days, 1 or 10 nmol/d, icv) or artificial cerebrospinal fluid (aCSF) using metabolic cages. High dose AgRP reduced body mass (aCSF n=12, +0.8±0.6 vs 1 nmol/d n=14, +0.6±0.6 vs 10 nmol/d n=11, -1.5±0.5 p<0.05 g/21d), without affecting food intake (15.1±1.2 vs 14.1±1.1 vs 16.3±1.1 kcal/d) or digestive efficiency (85.2±0.5 vs 84.5±0.7 vs 85.1±0.6 %), but a significant reduction in energy efficiency (+3.8±2.0 vs +2.7±2.8 vs -5.9±2.2 p<0.05 mg/kcal) indicated increased total EE. Next, we examined the effect of AgRP(82-132) (14 days, 1 nmol/d, icv) using a multiplexed system (Promethion, Sable). AgRP had no effect on body mass (25.1±1.2, n=8 vs 26.7±0.5, n=8), overall body composition (by NMR), heat production (Weir, 24h: 0.485±0.015 vs 0.490±0.022 kcal/h), or respiratory exchange ratio (0.88±0.01 vs 0.89±0.01). AgRP increased total food intake (10.1±0.6, n=8 vs 11.9±0.5, n=8, kcal/d, p=0.03) through a synergistic effect on number of meals and median meal mass. We conclude that AgRP (1-10 nmol/d, 2-3 wk, icv) infusion causes subtle changes in feeding behavior without effect on digestive efficiency. In contrast, EE is paradoxically increased by AgRP when infused at a high dose (10 nmol/d). We postulate that these differences may reflect differential accessibility of the peptide to relevant feeding vs autonomic control regions of the hypothalamus when infused into the cerebral ventricles, and/or compensatory increases in EE secondary to changes in feeding behavior. Future studies to deconvolute the role of AgRP in the control of EE in mice will require site-specific delivery of the peptide to relevant target regions or manipulation of its receptor in those regions. Funding: HL134850, HL084207

Author(s):  
Keisuke Fukumura ◽  
Kenshiro Shikano ◽  
Yuaki Narimatsu ◽  
Eiko Iwakoshi-Ukena ◽  
Megumi Furumitsu ◽  
...  

Abstract We recently identified a novel hypothalamic small protein, named neurosecretory protein GL (NPGL), which is involved in energy homeostasis in birds and mammals. However, whether the action of NPGL is influenced by nutritional composition remains unknown. Thus, we investigated the effect of chronic intracerebroventricular infusion of NPGL for 13 days on feeding behavior and body mass gain under a normal chow diet (NC), high-fat diet, high-sucrose diet (HSD), and medium-fat/medium-sucrose diet (MFSD) in rats. NPGL stimulated food intake of NC and MFSD, especially during the light period. By contrast, NPGL decreased body mass gain under NC and increased total white adipose tissue mass in HSD- and MFSD-fed rats. These data suggest that the effects of NPGL on feeding behavior, body mass gain, and fat accumulation depend on nutrient type. Among them, sucrose in diets seems to contribute to fat accumulation elicited by NPGL.


2020 ◽  
Vol 21 (22) ◽  
pp. 8606
Author(s):  
Shogo Moriwaki ◽  
Yuki Narimatsu ◽  
Keisuke Fukumura ◽  
Eiko Iwakoshi-Ukena ◽  
Megumi Furumitsu ◽  
...  

RFamide-related peptide-3 (RFRP-3), the mammalian ortholog of avian gonadotropin-inhibitory hormone (GnIH), plays a crucial role in reproduction. In the present study, we explored the other functions of RFRP-3 by investigating the effects of chronic intracerebroventricular infusion of RFRP-3 (6 nmol/day) for 13 days on energy homeostasis in lean male C57BL/6J mice. The infusion of RFRP-3 increased cumulative food intake and body mass. In addition, the masses of brown adipose tissue (BAT) and the liver were increased by the administration of RFRP-3, although the mass of white adipose tissue was unchanged. On the other hand, RFRP-3 decreased O2 consumption, CO2 production, energy expenditure, and core body temperature during a short time period in the dark phase. These results suggest that the increase in food intake and the decrease in energy expenditure contributed to the gain of body mass, including the masses of BAT and the liver. The present study shows that RFRP-3 regulates not only reproductive function, but also energy metabolism, in mice.


2011 ◽  
Vol 27 (6) ◽  
pp. 407-412 ◽  
Author(s):  
Peng-Hua Fang ◽  
Mei Yu ◽  
Yin-Ping Ma ◽  
Jian Li ◽  
Yu-Mei Sui ◽  
...  

1998 ◽  
Vol 76 (2) ◽  
pp. 237-241 ◽  
Author(s):  
L J Martin ◽  
PJH Jones ◽  
R V Considine ◽  
W Su ◽  
N F Boyd ◽  
...  

To investigate whether circulating leptin levels are associated with energy expenditure in healthy humans, doubly labeled water energy measurements and food intake assessment were carried out in 27 women (mean age, 48.6 years; weight, 61.9 kg; body mass index, 23.2). Energy expenditure was determined over 13 days. Food intake was measured by 7-day food records. Leptin was measured by radioimmunoassay. Leptin level was strongly associated with percentage body fat (r = 0.59; p < 0.001), fat mass (r = 0.60; p < 0.001), and body mass index (r = 0.41; p = 0.03), but no correlation was observed with energy expenditure (r = 0.02; p = 0.93). After controlling for percentage body fat, a positive association of leptin level with energy expenditure of marginal significance (p = 0.06) was observed. There were no significant univariate associations of age, physical activity, lean body mass, height, or dietary variables with leptin level. When controlling for body fat, a significant positive correlation was observed for percent energy from carbohydrate and negative correlations with dietary fat and alcohol intake. These findings confirm previous associations between leptin and body fat content and suggest a relationship between serum leptin and energy expenditure level in healthy humans.Key words: leptin, energy expenditure, body composition, diet.


2001 ◽  
Vol 280 (4) ◽  
pp. R1061-R1068 ◽  
Author(s):  
Eric S. Corp ◽  
Beatrice Gréco ◽  
J. Bradley Powers ◽  
Carrie L. Marín Bivens ◽  
George N. Wade

Central injections of neuropeptide Y (NPY) increase food intake in Syrian hamsters; however, the effect of NPY on sexual behavior in hamsters is not known nor are the receptor subtypes involved in feeding and sexual behaviors. We demonstrate that NPY inhibits lordosis duration in a dose-related fashion after lateral ventricular injection in ovariectomized, steroid-primed Syrian hamsters. Under the same conditions, we compared the effect of two receptor-differentiating agonists derived from peptide YY (PYY), PYY-(3–36) and [Leu31,Pro34]PYY, on lordosis duration and food intake. PYY-(3–36) produced a 91% reduction in lordosis duration at 0.24 nmol. [Leu31,Pro34]PYY was less potent, producing a reduction in lordosis duration (66%) only at 2.4 nmol. These results suggest NPY effects on estrous behavior are principally mediated by Y2 receptors. PYY-(3–36) and [Leu31,Pro34]PYY stimulated comparable dose-related increases in total food intake (2 h), suggesting Y5 receptors are involved in feeding. The significance of different NPY receptor subtypes controlling estrous and feeding behavior is highlighted by results on expression of Fos immunoreactivity (Fos-IR) elicited by either PYY-(3–36) or [Leu31,Pro34]PYY at a dose of each that differentiated between the two behaviors. Some differences were seen in the distribution of Fos-IR produced by the two peptides. Overall, however, the patterns of expression were similar. Our behavioral and anatomic results suggest that NPY-containing pathways controlling estrous and feeding behavior innervate similar nuclei, with the divergence in pathways controlling the separate behaviors characterized by linkage to different NPY receptor subtypes.


Appetite ◽  
2008 ◽  
Vol 50 (2-3) ◽  
pp. 562
Author(s):  
P. Lattimore ◽  
A. Roefs ◽  
A. Jansen ◽  
A.-K Fett ◽  
N. Geschwind ◽  
...  

2020 ◽  
Vol 223 (21) ◽  
pp. jeb231993
Author(s):  
Kimberley J. Mathot ◽  
Eva M. A. Kok ◽  
Piet van den Hout ◽  
Anne Dekinga ◽  
Theunis Piersma

ABSTRACTMass regulation in birds is well documented. For example, birds can increase body mass in response to lower availability and/or predictability of food and decrease body mass in response to increased predation danger. Birds also demonstrate an ability to maintain body mass across a range of food qualities. Although the adaptive significance of mass regulation has received a great deal of theoretical and empirical attention, the mechanisms by which birds achieve this have not. Several non-exclusive mechanisms could facilitate mass regulation in birds. Birds could regulate body mass by adjusting food intake (dieting), activity, baseline energetic requirements (basal metabolic rate), mitochondrial efficiency or assimilation efficiency. Here, we present the results of two experiments in captive red knots (Calidris canutus islandica) that assess three of these proposed mechanisms: dieting, activity and up- and down-regulation of metabolic rate. In the first experiment, knots were exposed to cues of predation risk that led them to exhibit presumably adaptive mass loss. In the second experiment, knots maintained constant body mass despite being fed alternating high- and low-quality diets. In both experiments, regulation of body mass was achieved through a combination of changes in food intake and activity. Both experiments also provide some evidence for a role of metabolic adjustments. Taken together, these two experiments demonstrate that fine-scale management of body mass in knots is achieved through multiple mechanisms acting simultaneously.


2020 ◽  
Vol 14 ◽  
Author(s):  
Helia Cheng ◽  
Schuyler J. Pablico ◽  
Jisu Lee ◽  
Ji Suk Chang ◽  
Sangho Yu

The central nervous system controls feeding behavior and energy expenditure in response to various internal and external stimuli to maintain energy balance. Here we report that the newly identified transcription factor zinc finger and BTB domain containing 16 (Zbtb16) is induced by energy deficit in the paraventricular (PVH) and arcuate (ARC) nuclei of the hypothalamus via glucocorticoid (GC) signaling. In the PVH, Zbtb16 is expressed in the anterior half of the PVH and co-expressed with many neuronal markers such as corticotropin-releasing hormone (Crh), thyrotropin-releasing hormone (Trh), oxytocin (Oxt), arginine vasopressin (Avp), and nitric oxide synthase 1 (Nos1). Knockdown (KD) of Zbtb16 in the PVH results in attenuated cold-induced thermogenesis and improved glucose tolerance without affecting food intake. In the meantime, Zbtb16 is predominantly expressed in agouti-related neuropeptide/neuropeptide Y (Agrp/Npy) neurons in the ARC and its KD in the ARC leads to reduced food intake. We further reveal that chemogenetic stimulation of PVH Zbtb16 neurons increases energy expenditure while that of ARC Zbtb16 neurons increases food intake. Taken together, we conclude that Zbtb16 is an important mediator that coordinates responses to energy deficit downstream of GCs by contributing to glycemic control through the PVH and feeding behavior regulation through the ARC, and additionally reveal its function in controlling energy expenditure during cold-evoked thermogenesis via the PVH. As a result, we hypothesize that Zbtb16 may be involved in promoting weight regain after weight loss.


2007 ◽  
Vol 192 (1) ◽  
pp. 3-15 ◽  
Author(s):  
David A Bechtold ◽  
Simon M Luckman

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.


2008 ◽  
Vol 295 (1) ◽  
pp. E78-E84 ◽  
Author(s):  
Sabine Strassburg ◽  
Stefan D. Anker ◽  
Tamara R. Castaneda ◽  
Lukas Burget ◽  
Diego Perez-Tilve ◽  
...  

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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