scholarly journals A novel satiety sensor detects circulating glucose and suppresses food consumption via insulin-producing cells in Drosophila

Cell Research ◽  
2020 ◽  
Author(s):  
Wei Qi ◽  
Gaohang Wang ◽  
Liming Wang
Keyword(s):  
Food Intake ◽  
Food Consumption ◽  
Energy Homeostasis ◽  
Animal Species ◽  
Suppressive Effect ◽  
Food Ingestion ◽  
Neural Regulation ◽  
Insulin Producing Cells ◽  
Survival Skill ◽  
Regulate Food Intake

AbstractSensing satiety is a crucial survival skill for all animal species including human. Despite the discovery of numerous neuromodulators that regulate food intake in Drosophila, the mechanism of satiety sensing remains largely elusive. Here, we investigated how neuropeptidergic circuitry conveyed satiety state to influence flies’ food consumption. Drosophila tackykinin (DTK) and its receptor TAKR99D were identified in an RNAi screening as feeding suppressors. Two pairs of DTK+ neurons in the fly brain could be activated by elevated D-glucose in the hemolymph and imposed a suppressive effect on feeding. These DTK+ neurons formed a two-synapse circuitry targeting insulin-producing cells, a well-known feeding suppressor, via TAKR99D+ neurons, and this circuitry could be rapidly activated during food ingestion and cease feeding. Taken together, we identified a novel satiety sensor in the fly brain that could detect specific circulating nutrients and in turn modulate feeding, shedding light on the neural regulation of 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 Serotonergic Neurons Translate Taste Detection into Internal Nutrient Regulation

2021 ◽  
Author(s):  
Zepeng Yao ◽  
Kristin Scott
Keyword(s):  
Food Intake ◽  
Sensory Neurons ◽  
Nutrient Availability ◽  
Energy Homeostasis ◽  
Enteric Neurons ◽  
Physiological Changes ◽  
Nutrient Regulation ◽  
Sensory Pathways ◽  
Insulin Producing Cells ◽  
Taste Detection

The nervous and endocrine systems coordinately monitor and regulate nutrient availability to maintain energy homeostasis. Sensory detection of food regulates internal nutrient availability in a manner that anticipates food intake, but sensory pathways that promote anticipatory physiological changes remain unclear. Here, we identify serotonergic (5-HT) neurons as critical mediators that transform gustatory detection by sensory neurons into the activation of insulin-producing cells and enteric neurons in Drosophila. One class of 5-HT neurons responds to gustatory detection of sugars, excites insulin-producing cells and limits consumption, suggesting that they anticipate increased nutrient levels and prevent overconsumption. A second class of 5-HT neurons responds to gustatory detection of bitter compounds and activates enteric neurons to promote gastric motility, likely to stimulate digestion and increase circulating nutrients when food quality is poor. These studies demonstrate that 5-HT neurons relay acute gustatory detection to divergent pathways for longer-term stabilization of circulating nutrients.

scholarly journals Peptides and proteins regulating food intake: a comparative view

2006 ◽  
Vol 56 (4) ◽  
pp. 447-473 ◽  
Author(s):  
Gert Flik ◽  
Mark Huising ◽  
Marnix Gorissen
Keyword(s):  
Energy Metabolism ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Homeostasis ◽  
Regulatory Mechanisms ◽  
Main Site ◽  
Recent Developments ◽  
Hypothalamic Arcuate Nucleus ◽  
Regulate Food Intake ◽  
Central Food

AbstractEnergy homeostasis is under multiple endocrine and neural controls that involve both central and peripheral hormones and neuropeptides. Disorders of energy balance (e.g., obesitas and anorexia nervosa) are caused by subtle dysregulation of these regulatory mechanisms. The hypothalamic arcuate nucleus is a main site of central regulation where two distinct subpopulations of neurons co-express either neuropeptide Y (NPY) and agouti-related protein (AgRP), or proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART): the former set of peptides increases food intake; the latter decreases food intake and affect energy metabolism. Key peripheral hormones affecting energy metabolism include cholecystokinin (CCK), leptin and insulin, which decrease food intake, and ghrelin, which increases food intake. CCK and ghrelin regulate food intake in the short term (by affecting meal size), whereas leptin and insulin regulate food intake over longer periods spanning several meals. These signals and their physiology are reasonably well understood in mammals. On the other hand, knowledge on energy metabolism in earlier vertebrates is scant. Recently characterised central food intake regulatory mechanisms in fish suggest that they operate in a manner similar to their mammalian counterparts. Peripheral mechanisms have been poorly studied outside mammals. The recent identification of leptin in several fish species provides new insights and opportunities to enhance our understanding of the regulation of food intake. Comparative analysis of these peripheral mechanisms may shed new light on the function and evolution of the mechanisms controlling energy homeostasis. In this review, we summarise recent developments in understanding of mechanisms and signals that regulate energy balance in mammals, and compare these to what we now know about their orthologues in earlier vertebrates, with a particular focus on bony fishes.

Aminoprocalcitonin-mediated suppression of feeding involves the hypothalamic melanocortin system

2013 ◽  
Vol 304 (12) ◽  
pp. E1251-E1262 ◽  
Author(s):  
Eva Tavares ◽  
Rosario Maldonado ◽  
Francisco J. Miñano
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Suppressive Effect ◽  
Neural Pathways ◽  
Peptidergic Neurons ◽  
Melanocortin System ◽  
Pomc Mrna ◽  
Calcitonin Receptors ◽  
Fasted Rats

Aminoprocalcitonin (N-PCT), a neuroendocrine peptide encoded by the calcitonin-I (CALC-I) gene, suppresses food intake when administered centrally in rats. However, the neural pathways underlying this effect remain unclear. N-PCT and calcitonin receptors (CT-R) have been identified in hypothalamic regions involved in energy homeostasis, including the arcuate nucleus (ARC). Here, we hypothesized an involvement of the hypothalamic ARC in mediating the anorexic effects of central N-PCT based on its content of peptidergic neurons involved in feeding and its expression of N-PCT and CT-R. Fasting strongly reduced expression of the N-PCT precursor gene CALC-I in the ARC, and central immunoneutralization of endogenous N-PCT increased food intake. Intracerebroventricular administration of N-PCT reduced food intake in fed and fasted rats, and its effect was attenuated by a neutralizing anti-N-PCT antibody. Immunohistochemistry for N-PCT showed that it is expressed in astrocytes and neurons in the ARC and is colocalized with anorexigenic proopiomelanocortin (POMC) neurons. Fasting reduced coexpression of N-PCT and POMC, and N-PCT administration activated hypothalamic neurons, including rostral POMC neurons. We also found that N-PCT stimulates POMC mRNA expression in fed and fasted rats, whereas it reduced the expression of orexigenic peptides neuropeptide Y (NPY) and agouti-related peptide (AgRP) only in fasted rats in which those mRNAs are normally elevated. Finally, we showed that the melanocortin-3/4 receptor antagonist SHU 9119 attenuates the intake-suppressive effect of N-PCT. These data demonstrate that hypothalamic N-PCT is involved in control of energy balance and that its anorexigenic effects are mediated through the melanocortin system.

scholarly journals Deficiency of TNFα Converting Enzyme (TACE/ADAM17) Causes a Lean, Hypermetabolic Phenotype in Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6053-6064 ◽  
Author(s):  
Richard W. Gelling ◽  
Wenbo Yan ◽  
Salwa Al-Noori ◽  
Aaron Pardini ◽  
Gregory J. Morton ◽  
...  
Keyword(s):  
Food Intake ◽  
System Integration ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Converting Enzyme ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Regulate Food Intake ◽  
Afferent Inputs ◽  
Deficient Mice

Energy homeostasis involves central nervous system integration of afferent inputs that coordinately regulate food intake and energy expenditure. Here, we report that adult homozygous TNFα converting enzyme (TACE)-deficient mice exhibit one of the most dramatic examples of hypermetabolism yet reported in a rodent system. Because this effect is not matched by increased food intake, mice lacking TACE exhibit a lean phenotype. In the hypothalamus of these mice, neurons in the arcuate nucleus exhibit intact responses to reduced fat mass and low circulating leptin levels, suggesting that defects in other components of the energy homeostasis system explain the phenotype of TaceΔZn/ΔZn mice. Elevated levels of uncoupling protein-1 in brown adipose tissue from TaceΔZn/ΔZn mice when compared with weight-matched controls suggest that deficient TACE activity is linked to increased sympathetic outflow. These findings collectively identify a novel and potentially important role for TACE in energy homeostasis.

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

2021 ◽  
Vol 118 (4) ◽  
pp. e2017218118
Author(s):  
Jessica Houtz ◽  
Guey-Ying Liao ◽  
Juan Ji An ◽  
Baoji Xu
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Neuronal Activity ◽  
Energy Homeostasis ◽  
Neurotrophin Receptor ◽  
Dorsomedial Hypothalamus ◽  
Adaptive Thermogenesis ◽  
Functional Implications ◽  
Regulate Food Intake ◽  
Raphe Pallidus

Mutations 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-fexpressing 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 (RPa) stimulates thermogenesis and increased energy expenditure, whereas DMHTrkB neurons that send collaterals to the paraventricular hypothalamus (PVH) and preoptic area (POA) 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.

Central Histamine, the H3-Receptor and Obesity Therapy

2019 ◽  
Vol 18 (7) ◽  
pp. 516-522
Author(s):  
Néstor F. Díaz ◽  
Héctor Flores-Herrera ◽  
Guadalupe García-López ◽  
Anayansi Molina-Hernández
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Animal Studies ◽  
Energy Homeostasis ◽  
Receptor Activation ◽  
Receptor Ligands ◽  
Histaminergic System ◽  
H3 Receptor ◽  
Weight One ◽  
The Central Nervous System

The brain histaminergic system plays a pivotal role in energy homeostasis, through H1- receptor activation, it increases the hypothalamic release of histamine that decreases food intake and reduces body weight. One way to increase the release of hypothalamic histamine is through the use of antagonist/inverse agonist for the H3-receptor. Histamine H3-receptors are auto-receptors and heteroreceptors located on the presynaptic membranes and cell soma of neurons, where they negatively regulate the synthesis and release of histamine and other neurotransmitters in the central nervous system. Although several compounds acting as H3-receptor antagonist/inverse agonists have been developed, conflicting results have been reported and only one has been tested as anti-obesity in humans. Animal studies revealed the opposite effect in food intake, energy expeditor, and body weight, depending on the drug, spice, and route of administration, among others. The present review will explore the state of art on the effects of H3-receptor ligands on appetite and body-weight, going through the following: a brief overview of the circuit involved in the control of food intake and energy homeostasis, the participation of the histaminergic system in food intake and body weight, and the H3-receptor as a potential therapeutic target for obesity.

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