scholarly journals Triiodothyronine Stimulates Food Intake via the Hypothalamic Ventromedial Nucleus Independent of Changes in Energy Expenditure

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5252-5258 ◽  
Author(s):  
Wing May Kong ◽  
Niamh M. Martin ◽  
Kirsty L. Smith ◽  
James V. Gardiner ◽  
Ian P. Connoley ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Fold Increase ◽  
Peripheral Circulation ◽  
Negative Energy ◽  
Early Gene ◽  
Ventromedial Nucleus ◽  
Mrna Levels ◽  
Iodothyronine Deiodinase ◽  
Nocturnal Feeding

Abstract Increased food intake is characteristic of hyperthyroidism, although this is presumed to compensate for a state of negative energy balance. However, here we show that the thyroid hormone T3 directly stimulates feeding at the level of the hypothalamus. Peripheral administration of T3 doubled food intake in ad libitum-fed rats over 2 h and induced expression of the immediate early gene, early growth response-1, in the hypothalamic ventromedial nucleus (VMN), whereas maintaining plasma-free T3 levels within the normal range. T3-induced feeding occurred without altering energy expenditure or locomotion. Injection of T3 directly into the VMN produced a 4-fold increase in food intake in the first hour. The majority of T3 in the brain is reported to be produced by tissue-specific conversion of T4 to T3 by the enzyme type 2 iodothyronine deiodinase (D2). Hypothalamic D2 mRNA expression showed a diurnal variation, with a peak in the nocturnal feeding phase. Hypothalamic D2 mRNA levels also increased after a 12- and 24-h fast, suggesting that local production of T3 may play a role in this T3 feeding circuit. Thus, we propose a novel hypothalamic feeding circuit in which T3, from the peripheral circulation or produced by local conversion, stimulates food intake via the VMN.

scholarly journals Antiobesity Effects of the β-Cell Hormone Amylin in Diet-Induced Obese Rats: Effects on Food Intake, Body Weight, Composition, Energy Expenditure, and Gene Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5855-5864 ◽  
Author(s):  
Jonathan D. Roth ◽  
Heather Hughes ◽  
Eric Kendall ◽  
Alain D. Baron ◽  
Christen M. Anderson
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Respiratory Quotient ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Lean Tissue ◽  
Reduced Body ◽  
Diet Induced Obesity ◽  
Cell Hormone

Effects of amylin and pair feeding (PF) on body weight and metabolic parameters were characterized in diet-induced obesity-prone rats. Peripherally administered rat amylin (300 μg/kg·d, 22d) reduced food intake and slowed weight gain: approximately 10% (P < 0.05), similar to PF. Fat loss was 3-fold greater in amylin-treated rats vs. PF (P < 0.05). Whereas PF decreased lean tissue (P < 0.05 vs. vehicle controls; VEH), amylin did not. During wk 1, amylin and PF reduced 24-h respiratory quotient (mean ± se, 0.82 ± 0.0, 0.81 ± 0.0, respectively; P < 0.05) similar to VEH (0.84 ± 0.01). Energy expenditure (EE mean ± se) tended to be reduced by PF (5.67 ± 0.1 kcal/h·kg) and maintained by amylin (5.86 ± 0.1 kcal/h·kg) relative to VEH (5.77 ± 0.0 kcal/h·kg). By wk 3, respiratory quotient no longer differed; however, EE increased with amylin treatment (5.74 ± 0.09 kcal/·kg; P < 0.05) relative to VEH (5.49 ± 0.06) and PF (5.38 ± 0.07 kcal/h·kg). Differences in EE, attributed to differences in lean mass, argued against specific amylin-induced thermogenesis. Weight loss in amylin and pair-fed rats was accompanied by similar increases arcuate neuropeptide Y mRNA (P < 0.05). Amylin treatment, but not PF, increased proopiomelanocortin mRNA levels (P < 0.05 vs. VEH). In a rodent model of obesity, amylin reduced body weight and body fat, with relative preservation of lean tissue, through anorexigenic and specific metabolic effects.

scholarly journals Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge eating disorder

2020 ◽  
Vol 45 (11) ◽  
pp. 1931-1941 ◽  
Author(s):  
Adele Romano ◽  
Maria Vittoria Micioni Di Bonaventura ◽  
Cristina Anna Gallelli ◽  
Justyna Barbara Koczwara ◽  
Dorien Smeets ◽  
...  
Keyword(s):  
Eating Disorder ◽  
Nucleus Accumbens ◽  
Food Intake ◽  
Binge Eating ◽  
Binge Eating Disorder ◽  
Female Rats ◽  
Early Gene ◽  
Mrna Levels ◽  
Palatable Food ◽  
Brain Areas

Abstract Binge eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell (“frustration stress”). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg−1) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior.

Peripheral and Central Glucocorticoid Signaling Contributes to Positive Energy Balance in Rats

2017 ◽  
Vol 49 (06) ◽  
pp. 472-479
Author(s):  
Tássia Borba ◽  
Lígia Galindo ◽  
Kelli Ferraz-Pereira ◽  
Raquel da Silva Aragão ◽  
Ana Toscano ◽  
...  
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Glucocorticoid Receptors ◽  
Negative Energy ◽  
Positive Energy ◽  
Obesity Epidemic ◽  
Routes Of Administration ◽  
Glucocorticoid Signaling ◽  
Positive Energy Balance

AbstractThe obesity epidemic has been the target of several studies to understand its etiology. The pathophysiological processes that take to obesity generally relate to the rupture of energy balance. This imbalance can result from environmental and/or endogenous events. Among the endogenous events, the hypothalamic-pituitary-adrenal axis, which promotes stress response via glucocorticoid activity, is considered a modulator of energy balance. However, it remains controversial whether the increase in plasma levels of glucocorticoids results in a positive or negative energy balance. Furthermore, there are no studies comparing different routes of administration of glucocorticoids in this context. Here, we investigated the effects of intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of a specific agonist for glucocorticoid receptors on food intake and energy expenditure in rats. Sixty-day old rats were treated with i.p. or i.c.v. dexamethasone. Food intake and satiety were evaluated, as well as locomotor activity in order to determine energy expenditure. Both i.p. and i.c.v. dexamethasone increased food intake and decreased energy expenditure. Moreover, i.c.v. dexamethasone delayed the onset of satiety. Together, these results confirm that central glucocorticoid signaling promotes a positive energy balance and supports the role of the glucocorticoid system as the underlying cause of psychological stress-induced obesity.

Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation

2010 ◽  
Vol 298 (3) ◽  
pp. E726-E734 ◽  
Author(s):  
Paulo José Forcina Martins ◽  
Marina Soares Marques ◽  
Sergio Tufik ◽  
Vânia D'Almeida
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Sleep Deprivation ◽  
Weight Control ◽  
Time Course ◽  
Energy Homeostasis ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Mrna Levels

Several pieces of evidence support that sleep duration plays a role in body weight control. Nevertheless, it has been assumed that, after the identification of orexins (hypocretins), the molecular basis of the interaction between sleep and energy homeostasis has been provided. However, no study has verified the relationship between neuropeptide Y (NPY) and orexin changes during hyperphagia induced by sleep deprivation. In the current study we aimed to establish the time course of changes in metabolite, endocrine, and hypothalamic neuropeptide expression of Wistar rats sleep deprived by the platform method for a distinct period (from 24 to 96 h) or sleep restricted for 21 days (SR-21d). Despite changes in the stress hormones, we found no changes in food intake and body weight in the SR-21d group. However, sleep-deprived rats had a 25–35% increase in their food intake from 72 h accompanied by slight weight loss. Such changes were associated with increased hypothalamus mRNA levels of prepro-orexin (PPO) at 24 h followed by NPY at 48 h of sleep deprivation. Conversely, sleep recovery reduced the expression of both PPO and NPY, which rapidly brought the animals to a hypophagic condition. Our data also support that sleep deprivation rapidly increases energy expenditure and therefore leads to a negative energy balance and a reduction in liver glycogen and serum triacylglycerol levels despite the hyperphagia. Interestingly, such changes were associated with increased serum levels of glucagon, corticosterone, and norepinephrine, but no effects on leptin, insulin, or ghrelin were observed. In conclusion, orexin activation accounts for the myriad changes induced by sleep deprivation, especially the hyperphagia induced under stress and a negative energy balance.

scholarly journals A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer’s Disease, the 5XFAD Mouse

2021 ◽  
Vol 22 (10) ◽  
pp. 5365
Author(s):  
Antonio J. López-Gambero ◽  
Cristina Rosell-Valle ◽  
Dina Medina-Vera ◽  
Juan Antonio Navarro ◽  
Antonio Vargas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Mouse Model ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
5Xfad Mouse ◽  
5Xfad Mice ◽  
Metabolic Dysfunctions

Increasing evidence links metabolic disorders with neurodegenerative processes including Alzheimer’s disease (AD). Late AD is associated with amyloid (Aβ) plaque accumulation, neuroinflammation, and central insulin resistance. Here, a humanized AD model, the 5xFAD mouse model, was used to further explore food intake, energy expenditure, neuroinflammation, and neuroendocrine signaling in the hypothalamus. Experiments were performed on 6-month-old male and female full transgenic (Tg5xFAD/5xFAD), heterozygous (Tg5xFAD/-), and non-transgenic (Non-Tg) littermates. Although histological analysis showed absence of Aβ plaques in the hypothalamus of 5xFAD mice, this brain region displayed increased protein levels of GFAP and IBA1 in both Tg5xFAD/- and Tg5xFAD/5xFAD mice and increased expression of IL-1β in Tg5xFAD/5xFAD mice, suggesting neuroinflammation. This condition was accompanied by decreased body weight, food intake, and energy expenditure in both Tg5xFAD/- and Tg5xFAD/5xFAD mice. Negative energy balance was associated with altered circulating levels of insulin, GLP-1, GIP, ghrelin, and resistin; decreased insulin and leptin hypothalamic signaling; dysregulation in main metabolic sensors (phosphorylated IRS1, STAT5, AMPK, mTOR, ERK2); and neuropeptides controlling energy balance (NPY, AgRP, orexin, MCH). These results suggest that glial activation and metabolic dysfunctions in the hypothalamus of a mouse model of AD likely result in negative energy balance, which may contribute to AD pathogenesis development.

Adolescent Inhalant Abuse Results in Adrenal Dysfunction and a Hypermetabolic Phenotype with Persistent Growth Impairments

2018 ◽  
Vol 107 (4) ◽  
pp. 340-354 ◽  
Author(s):  
Rose Crossin ◽  
Zane B. Andrews ◽  
Natalie A. Sims ◽  
Terence Pang ◽  
Michael Mathai ◽  
...  
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Adrenal Insufficiency ◽  
Fasting Blood Glucose ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Metabolic Phenotype ◽  
Adolescent Male ◽  
Inhalant Abuse

Background/Aims: Abuse of toluene products (e.g., glue-sniffing) primarily occurs during adolescence and has been associated with appetite suppression and weight impairments. However, the metabolic phenotype arising from adolescent inhalant abuse has never been fully characterised, and its persistence during abstinence and underlying mechanisms remain unknown. Methods: Adolescent male Wistar rats (post-natal day 27) were exposed to inhaled toluene (10,000 ppm) (n = 32) or air (n = 48) for 1 h/day, 3 days/week for 4 weeks, followed by 4 weeks of abstinence. Twenty air rats were pair-fed to the toluene group, to differentiate the direct effects of toluene from under-nutrition. Food intake, weight, and growth were monitored. Metabolic hormones were measured after exposure and abstinence periods. Energy expenditure was measured using indirect calorimetry. Adrenal function was assessed using adrenal histology and hormone testing. Results: Inhalant abuse suppressed appetite and increased energy expenditure. Reduced weight gain and growth were observed in both the toluene and pair-fed groups. Compared to the pair-fed group, and despite normalisation of food intake, the suppression of weight and growth for toluene-exposed rats persisted during abstinence. After exposure, toluene-exposed rats had low fasting blood glucose and insulin compared to the air and pair-fed groups. Consistent with adrenal insufficiency, adrenal hypertrophy and increased basal adrenocorticotropic hormone were observed in the toluene-exposed rats, despite normal basal corticosterone levels. Conclusions: Inhalant abuse results in negative energy balance, persistent growth impairment, and endocrine changes suggestive of adrenal insufficiency. We conclude that adrenal insufficiency contributes to the negative energy balance phenotype, potentially presenting a significant additional health risk for inhalant users.

scholarly journals Photoperiod effects on gene expression for hypothalamic appetite-regulating peptides and food intake in the ram

2003 ◽  
Vol 284 (1) ◽  
pp. R101-R115 ◽  
Author(s):  
Iain J. Clarke ◽  
Alexandra Rao ◽  
Yves Chilliard ◽  
Carole Delavaud ◽  
Gerald A. Lincoln
Keyword(s):  
Gene Expression ◽  
Energy Balance ◽  
Food Intake ◽  
Leptin Receptor ◽  
Negative Energy ◽  
Positive Energy ◽  
Mrna Levels ◽  
Expression Of Genes ◽  
Positive Energy Balance ◽  
Plasma Leptin

Relationship between voluntary food intake (VFI) and gene expression for appetite-regulating peptides was examined in the brains of Soay rams under contrasting photoperiods. Two groups ( n = 8) were subjected to alternating block long-day (LD) and short-day photoperiods (SD) over a period of 42 wk to entrain long-term cycles in VFI. Five animals from each group were killed 18 wk into LD or SD, and the brains were collected for in situ hybridization studies. VFI was fourfold higher under LD compared with SD. Body weight, abdominal fat, or plasma leptin levels were similar under LD and SD. LD animals were in positive energy balance and sexually inactive, and SD animals were in negative energy balance and sexually active. Neuropeptide Y (NPY) mRNA levels were higher in the arcuate nucleus (ARC) under LD, and pro-opiomelanocortin expression was lower under LD. Leptin receptor (Ob-Rb) was higher in the ARC under LD. We conclude that photoperiod-induced increase in VFI correlates with expression of NPY, but not with expression of genes for other putative orexigenic peptides. Ob-Rb gene expression is regulated by photoperiod.

scholarly journals Hypothalamic CB1 Cannabinoid Receptors Regulate Energy Balance in Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4136-4143 ◽  
Author(s):  
Pierre Cardinal ◽  
Luigi Bellocchio ◽  
Samantha Clark ◽  
Astrid Cannich ◽  
Matthias Klugmann ◽  
...  
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Receptor Gene ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Mrna Levels ◽  
Receptor Signaling ◽  
Brown Adipose ◽  
The Impact

Cannabinoid type 1 (CB1) receptor activation is generally considered a powerful orexigenic signal and inhibition of the endocannabinoid system is beneficial for the treatment of obesity and related metabolic diseases. The hypothalamus plays a critical role in regulating energy balance by modulating both food intake and energy expenditure. Although CB1 receptor signaling has been implicated in the modulation of both these mechanisms, a complete understanding of its role in the hypothalamus is still lacking. Here we combined a genetic approach with the use of adeno-associated viral vectors to delete the CB1 receptor gene in the adult mouse hypothalamus and assessed the impact of such manipulation on the regulation of energy balance. Viral-mediated deletion of the CB1 receptor gene in the hypothalamus led to the generation of Hyp-CB1-KO mice, which displayed an approximately 60% decrease in hypothalamic CB1 receptor mRNA levels. Hyp-CB1-KO mice maintained on a normocaloric, standard diet showed decreased body weight gain over time, which was associated with increased energy expenditure and elevated β3-adrenergic receptor and uncoupling protein-1 mRNA levels in the brown adipose tissue but, surprisingly, not to changes in food intake. Additionally, Hyp-CB1-KO mice were insensitive to the anorectic action of the hormone leptin (5 mg/kg) and displayed a time-dependent hypophagic response to the CB1 inverse agonist rimonabant (3 mg/kg). Altogether these findings suggest that hypothalamic CB1 receptor signaling is a key determinant of energy expenditure under basal conditions and reveal its specific role in conveying the effects of leptin and pharmacological CB1 receptor antagonism on food intake.

scholarly journals Synergistic Control of KNDy Neuronal Influence on Energy Balance by Ghrelin and Estradiol

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A554-A555
Author(s):  
Kristie M Conde ◽  
Danielle Kulyk ◽  
Troy Adam Roepke
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Negative Energy ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Meal Pattern ◽  
Kndy Neurons

Abstract The gut peptide, ghrelin, mediates negative energy homeostasis and the neuroendocrine control of energy homeostasis by acting through its receptor, growth hormone secretagogue receptor (GHSR). GHSR, expressed in hypothalamic Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons in the arcuate (ARC), is well known to regulate energy balance. We have previously shown 17-beta-estradiol (E2) robustly increases Ghsr expression in KNDy neurons, enhancing their sensitivity to ghrelin. We hypothesize that E2-induced increase in GHSR expression augments KNDy sensitivity in a fasting state by elevating ghrelin to reduce energy expenditure in females. We developed a Kiss1-specific GHSR knockout to determine the role of GHSR in ARC KNDy neurons and fed them either a low-fat diet (LFD) or a high-fat diet (HFD). Knockout (experimental) females were resistant to HFD in terms of body weight gain, adiposity, and food intake compared to HFD-fed controls. HFD-fed experimental females also exhibited slower glucose clearance compared to HFD-fed controls. Experimental females, regardless of diet, exhibited elevated fasting (5h) glucose. Metabolic rates (V.O2, V.CO2) and energy expenditure (heat) were not different. Respiratory Exchange Ratio (RER) was elevated in LFD-fed females, indicating the utilization of carbohydrates over fat for energy. Further meal pattern analysis revealed a reduction in meal duration in HFD-fed females, but elevated meal frequency, while HFD-fed experimental females exhibited a reduced meal size. In two separate meal pattern experiments, experimental and control females were fasted for 24h and refed or injected with ghrelin (I.P. 1mg/kg) or saline. We observed a striking delay in refeeding behavior in experimental females compared to controls during the refeeding period after fasting. After injection, control females responded to ghrelin with a rapid and sustained increase in food intake which was blunted in experimentals. Collectively, these data suggest that GHSR activation in KNDy neurons modulates metabolism, glucose homeostasis, and feeding behavior, illustrating a novel mechanism for E2 and ghrelin to synergistically control KNDy neuronal output and their subsequent behavioral and physiological outcomes.

scholarly journals The effects of enterostatin intake on food intake and energy expenditure

2003 ◽  
Vol 90 (1) ◽  
pp. 207-214 ◽  
Author(s):  
Eva M. R. Kovacs ◽  
Manuela P. G. M. Lejeune ◽  
Margriet S. Westerterp-Plantenga
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Resting Metabolic Rate ◽  
Body Weight Loss ◽  
Negative Energy ◽  
High Fat ◽  
Double Blind ◽  
Diet Induced Thermogenesis

Enterostatin (ENT) has been found to inhibit food intake and selectively inhibit fat intake in rats. Both peripheral and central mechanisms have been proposed. It also has been suggested that ENT may increase thermogenesis. The present study investigated the effects of oral ENT administration on food intake, energy expenditure and body weight in subjects with a preference for a high-fat diet. In a double-blind, placebo-controlled, randomized and crossover design, nine female and three male healthy subjects (age 34 (sd 11) years, BMI 24·5 (sd 2·5) kg/m2) with a preference for a high-fat diet ingested ENT (3 × 15 mg/d) or placebo (PLA) while consuming a high-fat diet ad libitum for 4d. Eight subjects ended each intervention with a 36h stay in the respiration chamber, continuing the diet and treatment. Body-weight loss was significant (ENT 0·8 (se 0·3) kg, P<0·05; PLA 1·3 (se 0·3) kg, P<0·001), but not different between treatments. There was no difference between treatments in total energy intake (ENT 37·1 (se 2·6), PLA 35·9 (se 3·2) MJ), macronutrient composition, hunger, satiety and hedonic scores during the 4d high-fat diet. Energy expenditure (24h) (ENT 9·6 (se 0·4), PLA 9·5 (se 0·4) MJ), sleeping and resting metabolic rate, diet-induced thermogenesis, activity-induced energy expenditure and 24h RQ (ENT 0·77 (se 0·01), PLA 0·77 (se 0·01)) were similar for both treatments. We conclude that oral ENT administration did not affect food intake, energy expenditure or body weight in subjects with a preference for a high-fat diet experiencing a negative energy and fat balance.

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