scholarly journals Activation of the NPY Y5 receptor regulates both feeding and energy expenditure

1999 ◽  
Vol 277 (5) ◽  
pp. R1428-R1434 ◽  
Author(s):  
Joyce J. Hwa ◽  
Melanie B. Witten ◽  
Patricia Williams ◽  
Lorraine Ghibaudi ◽  
Jun Gao ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Interscapular Brown Adipose Tissue ◽  
Peptide Analogs ◽  
Brown Adipose ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Intracerebroventricular (ICV) administration of neuropeptide Y (NPY) has been shown to decrease energy expenditure, induce hypothermia, and stimulate food intake. Recent evidence has suggested that the Y5 receptor may be a significant mediator of NPY-stimulated feeding. The present study attempts to further characterize the role of NPY Y5-receptor subtypes in feeding and energy expenditure regulation. Satiated Long-Evans rats with temperature transponders implanted in the interscapular brown adipose tissue (BAT) displayed a dose-dependent decrease in BAT temperature and an increase in food intake after ICV infusion of NPY. Similar effects were induced by ICV administration of peptide analogs of NPY that activate the Y5 receptor, but not by analogs that activate Y1, Y2, or Y4 receptors. Furthermore, ICV infusion of the Y5 selective agonistd-[Trp32]-NPY significantly reduced oxygen consumption and energy expenditure of rats as measured by indirect calorimetry. These data suggest that the NPY Y5-receptor subtype not only mediates the feeding response of NPY but also contributes to brown fat temperature and energy expenditure regulation.

Insulin and metabolic efficiency in rats. II. Effects of NE and cold exposure

1986 ◽  
Vol 251 (6) ◽  
pp. R1118-R1125
Author(s):  
T. J. Bartness ◽  
C. J. Billington ◽  
A. S. Levine ◽  
J. E. Morley ◽  
N. E. Rowland ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Energy Expenditure ◽  
Cold Exposure ◽  
Diabetic Rats ◽  
Metabolic Efficiency ◽  
Maximal Energy ◽  
Brown Adipose

The role of insulin in metabolic efficiency (ME, i.e., efficiency of body wt gain) was examined under conditions of maximal energy expenditure in control and diabetic rats. Long-lasting insulin was administered using a protocol that did not affect food intake and increased ME in both groups. Half the animals were injected chronically with norepinephrine (NE). NE alone in controls decreased body weight and ME and increased brown adipose tissue (BAT) growth, thermogenic potential [cytochrome c oxidase activity (COA)], and lipoprotein lipases (LPL) activity; however, in diabetics, body weight, ME, and food intake all decreased and only BAT LPL activity and DNA content increased. The combination of NE and insulin increased BAT protein and COA in diabetics; in controls, all BAT measures were further increased and ME was intermediate to that of either treatment alone. Cold exposure decreased body weight and ME, increased food intake and qualitatively produced similar increases in BAT growth, COA, and LPL activity in both controls and diabetics. In diabetics, combined cold exposure and insulin did not affect the increase in BAT growth or LPL activity resulting from either treatment alone, but in controls this combination decreased BAT growth and COA. It is concluded that, even under conditions of maximal energy expenditure, both extremes of basal insulin status result in decreased BAT growth and thermogenic potential, but have opposite effects on ME.

beta 3-Adrenergic-mediated suppression of leptin gene expression in rats

1997 ◽  
Vol 272 (6) ◽  
pp. E1031-E1036 ◽  
Author(s):  
H. Li ◽  
M. Matheny ◽  
P. J. Scarpace
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Food Intake ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Cgp 12177 ◽  
Rat Strain

To investigate the role of beta 3-adrenergic receptors in the suppression of leptin gene expression, we fasted F-344 rats to decrease leptin mRNA levels, refed the rats to stimulate leptin mRNA production, and examined the ability of the beta 3-adrenergic agonist CGP-12177 to prevent the rise in leptin mRNA levels. In the initial 2 h after CGP-12177 (0.75 mg/kg), there were significant reductions in both food consumption and leptin mRNA levels in epididymal, perirenal, and interscapular white adipose tissue. We were unable to detect leptin mRNA in interscapular brown adipose tissue (IBAT), whereas there was a significant increase in uncoupling protein mRNA levels in IBAT after CGP-12177. The suppression of leptin mRNA and food intake by CGP-12177 was confirmed in a second experiment using another rat strain, the F-344 x BN. Furthermore, refeeding after a period of fasting increased leptin mRNA, which was prevented by CGP-12177. These data indicate a role for beta 3-adrenergic-mediated regulation of leptin gene expression in nonmutant rodents and are consistent with other reports suggesting that beta 3-adrenergic agonists suppress food intake.

The role of exercise in thermogenesis and energy balance

1989 ◽  
Vol 67 (4) ◽  
pp. 402-409 ◽  
Author(s):  
Denis Richard ◽  
Serge Rivest
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Exercise Training ◽  
Female Rats ◽  
Male Rats ◽  
Brown Adipose ◽  
Term Energy

The role of exercise training in energy balance has been reviewed. Recent well-conducted studies showed that exercise may increase energy expenditure not only during the period of exercise itself but during the postexercise period as well. This notion of excess postexercise oxygen consumption (EPOC), which has been a controversial issue for many years, is now becoming a generally well-accepted concept, the consensus being that EPOC takes place following prolonged and strenuous exercise bouts. Besides, the role of EPOC in long-term energy balance remains to be determined. Long-term energy balance studies carried out in rats show that exercise affects energy balance by altering food intake and promoting energy expenditure. In male rats exercise causes a marked decrease in energy intake which contributes, in association with the expenditure of exercise itself, to retard lean and fat tissue growth. From the suppressed deposition of lean body mass, decreases in basal metabolic rate can be predicted in males. In female rats, exercise does not affect food intake; the lower energy gain of exercise-trained females results from the elevated expenditure rate associated with exercise itself. In both male and female rats, there is no evidence that exercise training affects energy expenditure other than during exercise itself unless the habitual feeding pattern of the rats is radically modified. The interactive effects of diet and exercise, which have to be further investigated in long-term energy balance, emerge as a promising area of research.Key words: exercise training, nutritional energetics, brown adipose tissue, diet-induced thermogenesis, body composition.

Lateral hypothalamus and sympathetic firing rate

1988 ◽  
Vol 255 (3) ◽  
pp. R507-R512 ◽  
Author(s):  
T. Sakaguchi ◽  
M. Takahashi ◽  
G. A. Bray
Keyword(s):  
Firing Rate ◽  
Lateral Hypothalamus ◽  
Sympathetic Nerves ◽  
Hypothalamic Area ◽  
Interscapular Brown Adipose Tissue ◽  
Gold Thioglucose ◽  
Brown Adipose ◽  
Bilateral Lesions ◽  
Dose Dependent ◽  
Lowered Body

Measurements of sympathetic firing rate have been made after the acute microinjection of glucose or insulin into the lateral hypothalamic area as well as after ablation of this area with locally injected gold thioglucose. Injection of glucose into the lateral hypothalamus (LH) produced a small but significant and dose-dependent reduction in the firing rate of efferent sympathetic nerves to interscapular brown adipose tissue. Injection of insulin into the same region produced a very short-lived increase in efferent sympathetic firing rate. Bilateral lesions in the lateral hypothalamus produced by microinjection and gold thioglucose lowered body weight more than sham injections into the LH of control animals. There was an increase in basal sympathetic firing rate at 3, 9, and 24 h after LH lesions. There was also an increase in firing rate at 1 and 3 days, but by 7 days firing rate had returned to control levels. The data support the hypothesis that LH lesions enhance sympathetic activity but show only very limited modulation by glucose or insulin.

scholarly journals The thermogenic effect of nesfatin-1 requires recruitment of the melanocortin system

2017 ◽  
Vol 235 (2) ◽  
pp. 111-122 ◽  
Author(s):  
Riccardo Dore ◽  
Luka Levata ◽  
Sogol Gachkar ◽  
Olaf Jöhren ◽  
Jens Mittag ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Heat Loss ◽  
Central Administration ◽  
Melanocortin System ◽  
Direct Calorimetry ◽  
Iodothyronine Deiodinase ◽  
Interscapular Brown Adipose Tissue ◽  
Peripheral Tissues ◽  
Dry Heat ◽  
Brown Adipose

Nesfatin-1 is a bioactive polypeptide expressed both in the brain and peripheral tissues and involved in the control of energy balance by reducing food intake. Central administration of nesfatin-1 significantly increases energy expenditure, as demonstrated by a higher dry heat loss; yet, the mechanisms underlying the thermogenic effect of central nesfatin-1 remain unknown. Therefore, in this study, we sought to investigate whether the increase in energy expenditure induced by nesfatin-1 is mediated by the central melanocortin pathway, which was previously reported to mediate central nesfatin-1´s effects on feeding and numerous other physiological functions. With the application of direct calorimetry, we found that intracerebroventricular nesfatin-1 (25 pmol) treatment increased dry heat loss and that this effect was fully blocked by simultaneous administration of an equimolar dose of the melanocortin 3/4 receptor antagonist, SHU9119. Interestingly, the nesfatin-1-induced increase in dry heat loss was positively correlated with body weight loss. In addition, as assessed with thermal imaging, intracerebroventricular nesfatin-1 (100 pmol) increased interscapular brown adipose tissue (iBAT) as well as tail temperature, suggesting increased heat production in the iBAT and heat dissipation over the tail surface. Finally, nesfatin-1 upregulated pro-opiomelanocortin and melanocortin 3 receptor mRNA expression in the hypothalamus, accompanied by a significant increase in iodothyronine deiodinase 2 and by a nonsignificant increase in uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha mRNA in the iBAT. Overall, we clearly demonstrate that nesfatin-1 requires the activation of the central melanocortin system to increase iBAT thermogenesis and, in turn, overall energy expenditure.

scholarly journals Susceptibility to diet induced obesity at thermoneutral conditions is independent of UCP1

2021 ◽  
Author(s):  
Sebastian Dieckmann ◽  
Akim Strohmeyer ◽  
Monja Willershaeuser ◽  
Stefanie Maurer ◽  
Wolfgang Wurst ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Knockout Mice ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Exon 2 ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Knockout Model

Objective Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity. However, studies investigating the role of UCP1 to protect against diet-induced obesity are controversial and rely on the phenotyping of a single constitutive UCP1-knockout model. To address this issue, we generated a novel UCP1-knockout model by Cre-mediated deletion of Exon 2 in the UCP1 gene. We studied the effect of constitutive UCP1 knockout on metabolism and the development of diet-induced obesity. Methods UCP1 knockout and wildtype mice were housed at 30°C and fed a control diet for 4-weeks followed by 8-weeks of high-fat diet. Body weight and food intake were monitored continuously over the course of the study and indirect calorimetry was used to determine energy expenditure during both feeding periods. Results Based on Western blot analysis, thermal imaging and noradrenaline test, we confirmed the lack of functional UCP1 in knockout mice. However, body weight gain, food intake and energy expenditure were not affected by deletion of UCP1 gene function during both feeding periods. Conclusion Conclusively, we show that UCP1 does not protect against diet-induced obesity at thermoneutrality. Further we introduce a novel UCP1-KO mouse enabling the generation of conditional UCP1-knockout mice to scrutinize the contribution of UCP1 to energy metabolism in different cell types or life stages.

scholarly journals Social Isolation: How Can the Effects on the Cholinergic System Be Isolated?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jaromir Myslivecek
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Social Isolation ◽  
Cholinergic System ◽  
System Response ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Cholinergic Signaling ◽  
The Central Nervous System

Social species form organizations that support individuals because the consequent social behaviors help these organisms survive. The isolation of these individuals may be a stressor. We reviewed the potential mechanisms of the effects of social isolation on cholinergic signaling and vice versa how changes in cholinergic signaling affect changes due to social isolation.There are two important problems regarding this topic. First, isolation schemes differ in their duration (1–165 days) and initiation (immediately after birth to adulthood). Second, there is an important problem that is generally not considered when studying the role of the cholinergic system in neurobehavioral correlates: muscarinic and nicotinic receptor subtypes do not differ sufficiently in their affinity for orthosteric site agonists and antagonists. Some potential cholinesterase inhibitors also affect other targets, such as receptors or other neurotransmitter systems. Therefore, the role of the cholinergic system in social isolation should be carefully considered, and multiple receptor systems may be involved in the central nervous system response, although some subtypes are involved in specific functions. To determine the role of a specific receptor subtype, the presence of a specific subtype in the central nervous system should be determined using search in knockout studies with the careful application of specific agonists/antagonists.

scholarly journals Knockout of inositol-requiring enzyme 1α in pro-opiomelanocortin neurons decreases fat mass via increasing energy expenditure

Open Biology ◽  
2016 ◽  
Vol 6 (8) ◽  
pp. 160131 ◽  
Author(s):  
Yuzhong Xiao ◽  
Tingting Xia ◽  
Junjie Yu ◽  
Yalan Deng ◽  
Hao Liu ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Metabolic Diseases ◽  
Critical Role ◽  
Liver Steatosis ◽  
Leptin Resistance ◽  
Hormone Production ◽  
Melanocyte Stimulating Hormone ◽  
Diet Induced Obesity ◽  
Brown Adipose

Although numerous functions of inositol-requiring enzyme 1α (IRE1α) have been identified, a role of IRE1α in pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus is largely unknown. Here, we showed that mice lacking IRE1α specifically in POMC neurons (PIKO) are lean and resistant to high-fat diet-induced obesity and obesity-related insulin resistance, liver steatosis and leptin resistance. Furthermore, PIKO mice had higher energy expenditure, probably due to increased thermogenesis in brown adipose tissue. Additionally, α-melanocyte-stimulating hormone production was increased in the hypothalamus of PIKO mice. These results demonstrate that IRE1α in POMC neurons plays a critical role in the regulation of obesity and obesity-related metabolic disorders. Our results also suggest that IRE1α is not only an endoplasmic reticulum stress sensor, but also a new potential therapeutic target for obesity and obesity-related metabolic diseases.

Abstract 424: Activation of the S1P3 Receptors is Responsible for S1P-mediated RhoA Activation and Cardioprotection

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Bryan S Yung ◽  
Sunny Y Xiang ◽  
Nicole Purcell ◽  
Hugh Rosen ◽  
Jerold Chun ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Cardiovascular Responses ◽  
Neonatal Rat ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
S1p Receptors ◽  
Rhoa Activation ◽  
Therapeutic Benefits

Sphingosine-1-phoshpate (S1P) is a bioactive lysophospholipid, generated and released at sites of tissue injury. S1P signals through a variety of G-protein coupled receptor subtypes and there are three major sub-types, S1P 1 , S1P 2 , and S1P 3 , to mediate cardiovascular responses. S1P 2 and S1P 3 receptors couple to Gα i , Gα 12 , Gα 13 and Gα q and we first examined the contribution of S1P 2 and S1P 3 to cardiac hypertrophy using S1P 2 and S1P 3 knockout (KO) mice and found that there is no difference in hypertrophy induced by pressure-overload. We previously showed that S1P provides cardioprotection against oxidative stress such as ischemia/reperfusion in which RhoA activation and its downstream effector PKD1 play an important role. It has not, however, been determined which S1P receptor subtype is responsible for S1P mediated cardioprotection. We knocked down the three major S1P receptors using siRNA in neonatal rat ventricular myocytes (NRVMs) and assessed RhoA and PKD1 activation induced by S1P. Knockdown of S1P 3 abolished RhoA activation and largely attenuated phosphorylation of PKD1 while knockdown of S1P 1 and S1P 2 did not. Using siRNA or pertussis toxin to inhibit different G-proteins, we further established that S1P regulates RhoA activation through Gα 13 , but not Gα 12 , Gα q , or Gα i . To investigate the role of S1P 3 receptors in the adult heart, hearts were isolated from wild-type or S1P 3 KO adult mice, perfused in the Langendorff mode and subjected to ex vivo ischemia/reperfusion. As previously reported, S1P perfusion significantly reduced infarct size induced by ischemia/reperfusion in WT hearts (by 50%), but this protection was abolished in the S1P 3 KO mouse heart. To further confirm the role of S1P 3 in cardioprotection we perfused WT mouse hearts with an S1P 3 -specific agonist CYM-51736. We observed that CYM-51736 attenuated the infarct size to a similar degree as that observed with S1P. Our findings reveal that activation of the S1P 3 receptor coupling to Gα 13 and subsequent RhoA activation is responsible for cardioprotection against ischemia/reperfusion. Accordingly specific drug targeting of S1P 3 receptors could provide therapeutic benefits in ischemic heart disease without the undesirable effects of global activation of other cardiac S1P receptors.

scholarly journals Effects of Chronic Intracerebroventricular Infusion of RFamide-Related Peptide-3 on Energy Metabolism in Male Mice

2020 ◽  
Vol 21 (22) ◽  
pp. 8606
Author(s):  
Shogo Moriwaki ◽  
Yuki Narimatsu ◽  
Keisuke Fukumura ◽  
Eiko Iwakoshi-Ukena ◽  
Megumi Furumitsu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Food Intake ◽  
Energy Expenditure ◽  
Body Mass ◽  
The Other ◽  
Related Peptide ◽  
Intracerebroventricular Infusion ◽  
Brown Adipose ◽  
The Masses

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.

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