scholarly journals Arcuate nucleus and lateral hypothalamic CART neurons in the mouse brain exert opposing effects on energy expenditure

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Aitak Farzi ◽  
Jackie Lau ◽  
Chi Kin Ip ◽  
Yue Qi ◽  
Yan-Chuan Shi ◽  
...  
Keyword(s):  
Physical Activity ◽  
Food Intake ◽  
Energy Expenditure ◽  
Lateral Hypothalamus ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Neuronal Populations ◽  
Neuron Activation ◽  
Important Regulator ◽  
Opposing Effects

Cocaine- and amphetamine-regulated transcript (CART) is widely expressed in the hypothalamus and an important regulator of energy homeostasis; however, the specific contributions of different CART neuronal populations to this process are not known. Here, we show that depolarization of mouse arcuate nucleus (Arc) CART neurons via DREADD technology decreases energy expenditure and physical activity, while it exerts the opposite effects in CART neurons in the lateral hypothalamus (LHA). Importantly, when stimulating these neuronal populations in the absence of CART, the effects were attenuated. In contrast, while activation of CART neurons in the LHA stimulated feeding in the presence of CART, endogenous CART inhibited food intake in response to Arc CART neuron activation. Taken together, these results demonstrate anorexigenic but anabolic effects of CART upon Arc neuron activation, and orexigenic but catabolic effects upon LHA-neuron activation, highlighting the complex and nuclei-specific functions of CART in controlling feeding and energy homeostasis.

scholarly journals Cold-induced hyperphagia requires AgRP-neuron activation in mice

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jennifer Deem ◽  
Chelsea L Faber ◽  
Christian Pedersen ◽  
Bao Anh Phan ◽  
Sarah A Larsen ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Cold Exposure ◽  
Energy Homeostasis ◽  
Cold Environment ◽  
Energy Demands ◽  
Acute Cold Exposure ◽  
Neuron Activation ◽  
Increase Food Intake

To maintain energy homeostasis during cold exposure, the increased energy demands of thermogenesis must be counterbalanced by increased energy intake. To investigate the neurobiological mechanisms underlying this cold-induced hyperphagia, we asked whether agouti-related peptide (AgRP) neurons are activated when animals are placed in a cold environment and, if so, whether this response is required for the associated hyperphagia. We report that AgRP-neuron activation occurs rapidly upon acute cold exposure, as do increases of both energy expenditure and energy intake, suggesting the mere perception of cold is sufficient to engage each of these responses. We further report that silencing of AgRP neurons selectively blocks the effect of cold exposure to increase food intake but has no effect on energy expenditure. Together, these findings establish a physiologically important role for AgRP neurons in the hyperphagic response to cold exposure.

scholarly journals Cold-induced hyperphagia requires AgRP neuron activation in mice

2020 ◽  
Author(s):  
Jennifer D. Deem ◽  
Chelsea L. Faber ◽  
Christian Pedersen ◽  
Bao Anh Phan ◽  
Sarah A. Larsen ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Cold Exposure ◽  
Energy Homeostasis ◽  
Cold Environment ◽  
Energy Demands ◽  
Acute Cold Exposure ◽  
Neuron Activation ◽  
Increase Food Intake

ABSTRACTTo maintain energy homeostasis during cold exposure, the increased energy demands of thermogenesis must be counterbalanced by increased energy intake. To investigate the neurobiological mechanisms underlying this cold-induced hyperphagia, we asked whether agouti-related peptide (AgRP) neurons are activated when animals are placed in a cold environment and, if so, whether this response is required for the associated hyperphagia. We report that AgRP-neuron activation occurs rapidly upon acute cold exposure, as do increases of both energy expenditure and energy intake, suggesting the mere perception of cold is sufficient to engage each of these responses. We further report that silencing of AgRP neurons selectively blocks the effect of cold exposure to increase food intake. Together, these findings establish a physiologically important role for AgRP neurons in the hyperphagic response to cold exposure.

scholarly journals Direct modulation of GFAP-expressing glia in the arcuate nucleus bi-directionally regulates feeding

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Naiyan Chen ◽  
Hiroki Sugihara ◽  
Jinah Kim ◽  
Zhanyan Fu ◽  
Boaz Barak ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Glial Activation ◽  
Inhibitory Input ◽  
Neuronal Populations ◽  
Structural Connections ◽  
Neuronal Subtype ◽  
Agouti Related Protein

Multiple hypothalamic neuronal populations that regulate energy balance have been identified. Although hypothalamic glia exist in abundance and form intimate structural connections with neurons, their roles in energy homeostasis are less known. Here we show that selective Ca2+ activation of glia in the mouse arcuate nucleus (ARC) reversibly induces increased food intake while disruption of Ca2+ signaling pathway in ARC glia reduces food intake. The specific activation of ARC glia enhances the activity of agouti-related protein/neuropeptide Y (AgRP/NPY)-expressing neurons but induces no net response in pro-opiomelanocortin (POMC)-expressing neurons. ARC glial activation non-specifically depolarizes both AgRP/NPY and POMC neurons but a strong inhibitory input to POMC neurons balances the excitation. When AgRP/NPY neurons are inactivated, ARC glial activation fails to evoke any significant changes in food intake. Collectively, these results reveal an important role of ARC glia in the regulation of energy homeostasis through its interaction with distinct neuronal subtype-specific pathways.

scholarly journals Gqα/G11α deficiency in dorsomedial hypothalamus leads to obesity resulting from decreased energy expenditure and impaired sympathetic nerve activity

2020 ◽  
Author(s):  
Eric A. Wilson ◽  
Hui Sun ◽  
Zhenzhong Cui ◽  
Marshal T. Jahnke ◽  
Mritunjay Pandey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Food Intake ◽  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Dorsomedial Hypothalamus ◽  
Ambient Temperatures ◽  
Brown Adipose ◽  
Inhibit Food Intake ◽  
Specific Deletion

The G protein subunits Gqα and G11α (Gq/11α) couple receptors to phospholipase C, leading to increased intracellular calcium. In this study we investigated the consequences of Gq/11α deficiency in the dorsomedial hypothalamus (DMH), a critical site for the control of energy homeostasis. Mice with DMH-specific deletion of Gq/11α (DMHGq/11KO) were generated by stereotaxic injection of AAV-Cre-GFP into the DMH of Gqαflox/flox:G11α-/- mice. Compared to control mice that received DMH injection of AAV-GFP, DMHGq/11KO mice developed obesity associated with reduced energy expenditure without significant changes in food intake or physical activity. DMHGq/11KO mice showed no defects in the ability of the melanocortin agonist melanotan II to acutely stimulate energy expenditure or to inhibit food intake. At room temperature (22oC) DMHGq/11KO mice showed reduced sympathetic nervous system activity in brown adipose tissue (BAT) and heart, accompanied with decreased basal BAT Ucp1 gene expression and lower heart rates. These mice were cold intolerant when acutely exposed to cold (6oC for 5 hours) and had decreased cold-stimulated BAT Ucp1 gene expression. DMHGq/11KO mice also failed to adapt to gradually declining ambient temperatures and to develop adipocyte browning in inguinal white adipose tissue although their BAT Ucp1 was proportionally stimulated. Consistent with impaired cold-induced thermogenesis, the onset of obesity in DMHGq/11KO mice was significantly delayed when housed under thermoneutral conditions (30ºC). Thus, our results show that Gqα and G11α in the DMH are required for the control of energy homeostasis by stimulating energy expenditure and thermoregulation.

scholarly journals Endocrine factors in the hypothalamic regulation of food intake in females: a review of the physiological roles and interactions of ghrelin, leptin, thyroid hormones, oestrogen and insulin

2011 ◽  
Vol 24 (1) ◽  
pp. 132-154 ◽  
Author(s):  
V. Somogyi ◽  
A. Gyorffy ◽  
T. J. Scalise ◽  
D. S. Kiss ◽  
G. Goszleth ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Thyroid Hormones ◽  
Energy Homeostasis ◽  
The Body ◽  
Feedback Information ◽  
Hypothalamic Regulation ◽  
The Individual ◽  
Desire To Eat ◽  
The Brain

Controlling energy homeostasis involves modulating the desire to eat and regulating energy expenditure. The controlling machinery includes a complex interplay of hormones secreted at various peripheral endocrine endpoints, such as the gastrointestinal tract, the adipose tissue, thyroid gland and thyroid hormone-exporting organs, the ovary and the pancreas, and, last but not least, the brain itself. The peripheral hormones that are the focus of the present review (ghrelin, leptin, thyroid hormones, oestrogen and insulin) play integrated regulatory roles in and provide feedback information on the nutritional and energetic status of the body. As peripheral signals, these hormones modulate central pathways in the brain, including the hypothalamus, to influence food intake, energy expenditure and to maintain energy homeostasis. Since the growth of the literature on the role of various hormones in the regulation of energy homeostasis shows a remarkable and dynamic expansion, it is now becoming increasingly difficult to understand the individual and interactive roles of hormonal mechanisms in their true complexity. Therefore, our goal is to review, in the context of general physiology, the roles of the five best-known peripheral trophic hormones (ghrelin, leptin, thyroid hormones, oestrogen and insulin, respectively) and discuss their interactions in the hypothalamic regulation of food intake.

scholarly journals Oxytocin Secretion Is Related to Measures of Energy Homeostasis in Young Amenorrheic Athletes

2014 ◽  
Vol 99 (5) ◽  
pp. E881-E885 ◽  
Author(s):  
Elizabeth A. Lawson ◽  
Kathryn E. Ackerman ◽  
Meghan Slattery ◽  
Dean A. Marengi ◽  
Hannah Clarke ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Growth Factor ◽  
Food Intake ◽  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Female Athletes ◽  
Young Female ◽  
Fibroblast Growth Factor 21 ◽  
Energy Availability ◽  
Fibroblast Growth

Context: Oxytocin has been implicated in the modulation of energy metabolism in animals. Oxytocin knockout mice develop obesity without a change in food intake, suggesting that a lack of oxytocin may reduce metabolic rate. Furthermore, administration of oxytocin centrally reduces food intake in rats, an effect reversed by an oxytocin antagonist, implying that oxytocin may regulate appetite and energy intake. We have previously demonstrated that young female athletes (in a higher energy expenditure state than nonathletes) have low nocturnal oxytocin compared with nonathletes. Whether oxytocin is associated with measures of energy homeostasis in athletes is unknown. Objective: We hypothesized that oxytocin, a signal for energy availability, would be associated with other measures of energy homeostasis in young female athletes. Design and Setting: We performed a cross-sectional study of 45 females, aged 14–21 years [15 amenorrheic athletes (AA), 15 eumenorrheic athletes, and 15 nonathletes] of comparable body mass index. Methods: Dual x-ray absorptiometry was performed to assess body composition. Indirect calorimetry was used to measure resting energy expenditure (REE). Fasting levels of oxytocin, energy homeostasis hormones irisin and fibroblast growth factor-21, and appetite-regulating hormone peptide YY were obtained. Results: In AA, oxytocin secretion was positively correlated with surrogate measures of energy availability, including weight (r = 0.65, P = .009) and body mass index (r = 0.61, P = .016). Furthermore, oxytocin was associated with REE (r = 0.80, P = .0003), independent of lean mass, and with irisin (r = 0.74, P = .002) and fibroblast growth factor-21 (r = 0.58, P = .024). In eumenorrheic athletes, oxytocin was associated with REE (r = 0.59, P = .021), independent of lean mass. In nonathletes, oxytocin secretion was not significantly associated with measures of energy homeostasis. Conclusions: In AA, oxytocin secretion is associated with measures of energy availability and expenditure, suggesting that oxytocin may be involved in regulation of energy balance in energy deficient states. Further studies determining the role of oxytocin in appetite and energy homeostasis in athletes are warranted.

scholarly journals PDK1-Foxo1 in Agouti-Related Peptide Neurons Regulates Energy Homeostasis by Modulating Food Intake and Energy Expenditure

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18324 ◽  
Author(s):  
Yongheng Cao ◽  
Masanori Nakata ◽  
Shiki Okamoto ◽  
Eisuke Takano ◽  
Toshihiko Yada ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Related Peptide

scholarly journals The Melanocortin Receptor Accessory Protein 2 promotes food intake through inhibition of the Prokineticin Receptor-1

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Anna L Chaly ◽  
Dollada Srisai ◽  
Ellen E Gardner ◽  
Julien A Sebag
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Severe Obesity ◽  
Melanocortin Receptor ◽  
Accessory Protein ◽  
Important Regulator ◽  
Receptor Accessory Protein

The Melanocortin Receptor Accessory Protein 2 (MRAP2) is an important regulator of energy homeostasis and its loss causes severe obesity in rodents. MRAP2 mediates its action in part through the potentiation of the MC4R, however, it is clear that MRAP2 is expressed in tissues that do not express MC4R, and that the deletion of MRAP2 does not recapitulate the phenotype of Mc4r KO mice. Consequently, we hypothesized that other GPCRs involved in the control of energy homeostasis are likely to be regulated by MRAP2. In this study we identified PKR1 as the first non-melanocortin GPCR to be regulated by MRAP2. We show that MRAP2 significantly and specifically inhibits PKR1 signaling. We also demonstrate that PKR1 and MRAP2 co-localize in neurons and that Mrap2 KO mice are hypersensitive to PKR1 stimulation. This study not only identifies new partners of MRAP2 but also a new pathway through which MRAP2 regulates energy homeostasis.

scholarly journals Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

2020 ◽  
Author(s):  
Jessica Houtz ◽  
Guey-Ying Liao ◽  
Baoji Xu
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Neuronal Activity ◽  
Energy Homeostasis ◽  
Preoptic Area ◽  
Neurotrophin Receptor ◽  
Dorsomedial Hypothalamus ◽  
Adaptive Thermogenesis ◽  
Regulate Food Intake ◽  
Raphe Pallidus

AbstractMutations in the TrkB neurotrophin receptor lead to profound obesity in humans, and expression of TrkB in the dorsomedial hypothalamus (DMH) is critical for maintaining energy homeostasis. However, the functional implications of TrkB-expressing neurons in the DMH (DMHTrkB) on energy expenditure are unclear. Additionally, the neurocircuitry underlying the effect of DMHTrkB neurons on energy homeostasis has not been explored. In this study, we show that activation of DMHTrkB neurons leads to a robust increase in adaptive thermogenesis and energy expenditure without altering heart rate or blood pressure, while silencing DMHTrkB neurons impairs thermogenesis. Furthermore, we reveal neuroanatomically and functionally distinct populations of DMHTrkB neurons that regulate food intake or thermogenesis. Activation of DMHTrkB neurons projecting to the raphe pallidus stimulates thermogenesis and increased energy expenditure, whereas DMHTrkB neurons that send collaterals to the paraventricular hypothalamus and preoptic area inhibit feeding. Together, our findings provide evidence that DMHTrkB neuronal activity plays an important role in regulating energy expenditure and delineate distinct neurocircuits that underly the separate effects of DMHTrkB neuronal activity on food intake and thermogenesis.Brief summaryThis study shows that TrkB-expressing DMH neurons stimulate thermogenesis through projection to raphe pallidus, while inhibiting feeding through collaterals to paraventricular hypothalamus and preoptic area.

scholarly journals Involvement of the Acyl-CoA binding domain containing 7 in the control of food intake and energy expenditure in mice

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Damien Lanfray ◽  
Alexandre Caron ◽  
Marie-Claude Roy ◽  
Mathieu Laplante ◽  
Fabrice Morin ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Arcuate Nucleus ◽  
Binding Domain ◽  
Nucleotide Polymorphism ◽  
Melanocortin System ◽  
Single Nucleotide ◽  
Hypothalamic Arcuate Nucleus ◽  
Paralog Gene ◽  
G Protein Coupled

Acyl-CoA binding domain-containing 7 (Acbd7) is a paralog gene of the diazepam-binding inhibitor/Acyl-CoA binding protein in which single nucleotide polymorphism has recently been associated with obesity in humans. In this report, we provide converging evidence indicating that a splice variant isoform of the Acbd7 mRNA is expressed and translated by some POMC and GABAergic-neurons in the hypothalamic arcuate nucleus (ARC). We have demonstrated that the ARC ACBD7 isoform was produced and processed into a bioactive peptide referred to as nonadecaneuropeptide (NDN) in response to catabolic signals. We have characterized NDN as a potent anorexigenic signal acting through an uncharacterized endozepine G protein-coupled receptor and subsequently via the melanocortin system. Our results suggest that ACBD7-producing neurons participate in the hypothalamic leptin signalling pathway. Taken together, these data suggest that ACBD7-producing neurons are involved in the hypothalamic control exerted on food intake and energy expenditure by the leptin-melanocortin pathway.

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