Regulation of food intake by mechanosensory ion channels in enteric neurons

Regulation of food intake is fundamental to energy homeostasis in animals. The contribution of non-nutritive and metabolic signals in regulating feeding is unclear. Here we show that enteric neurons play a major role in regulating feeding through specialized mechanosensory ion channels in Drosophila. Modulating activities of a specific subset of enteric neurons, the posterior enteric neurons (PENs), results in sixfold changes in food intake. Deficiency of the mechanosensory ion channel PPK1 gene or RNAi knockdown of its expression in the PENS result in a similar increase in food intake, which can be rescued by expression of wild-type PPK1 in the same neurons. Finally, pharmacological inhibition of the mechanosensory ion channel phenocopies the result of genetic interrogation. Together, our study provides the first molecular genetic evidence that mechanosensory ion channels in the enteric neurons are involved in regulating feeding, offering an enticing alternative to current therapeutic strategy for weight control.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00660.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. E726-E734 ◽

Cited By ~ 60

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.

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Serotonergic Neurons Translate Taste Detection into Internal Nutrient Regulation

10.1101/2021.05.13.444014 ◽

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.

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Author response: Regulation of food intake by mechanosensory ion channels in enteric neurons

10.7554/elife.04402.006 ◽

2014 ◽

Cited By ~ 1

Author(s):

William H Olds ◽

Tian Xu

Keyword(s):

Ion Channels ◽

Food Intake ◽

Enteric Neurons ◽

Author Response

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A high-protein total diet replacement alters the regulation of food intake and energy homeostasis in healthy, normal-weight adults

European Journal of Nutrition ◽

10.1007/s00394-021-02747-1 ◽

2021 ◽

Author(s):

Camila L. P. Oliveira ◽

Normand G. Boulé ◽

Sarah A. Elliott ◽

Arya M. Sharma ◽

Mario Siervo ◽

...

Keyword(s):

Energy Balance ◽

Food Intake ◽

Weight Control ◽

Energy Homeostasis ◽

Normal Weight ◽

High Protein ◽

Whole Body ◽

Blood Levels ◽

Total Diet ◽

The Impact

Abstract Purpose Dietary intake can affect energy homeostasis and influence body weight control. The aim of this study was to compare the impact of high-protein total diet replacement (HP-TDR) versus a control (CON) diet in the regulation of food intake and energy homeostasis in healthy, normal-weight adults. Methods In this acute randomized controlled, cross-over study, participants completed two isocaloric arms: a) HP-TDR: 35% carbohydrate, 40% protein, and 25% fat; b) CON: 55% carbohydrate, 15% protein, and 30% fat. The diets were provided for 32 h while inside a whole-body calorimetry unit. Appetite sensations, appetite-related hormones, and energy metabolism were assessed. Results Forty-three healthy, normal-weight adults (19 females) participated. Appetite sensations did not differ between diets (all p > 0.05). Compared to the CON diet, the change in fasting blood markers during the HP-TDR intervention was smaller for peptide tyrosine-tyrosine (PYY; − 18.9 ± 7.9 pg/mL, p = 0.02) and greater for leptin (1859 ± 652 pg/mL, p = 0.007). Moreover, postprandial levels of glucagon-like peptide 1 (1.62 ± 0.36 pM, p < 0.001) and PYY (31.37 ± 8.05 pg/mL, p < 0.001) were higher in the HP-TDR. Significant correlations were observed between energy balance and satiety (r = − 0.41, p = 0.007), and energy balance and PFC (r = 0.33, p = 0.033) in the HP-TDR. Conclusion Compared to the CON diet, the HP-TDR increased blood levels of anorexigenic hormones. Moreover, females and males responded differently to the intervention in terms of appetite sensations and appetite-related hormones. Trial registration NCT02811276 (retrospectively registered on 16 June 2016) and NCT03565510 (retrospectively registered on 11 June 2018).

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Ion Channel Dysfunction and Neuroinflammation in Migraine and Depression

Frontiers in Pharmacology ◽

10.3389/fphar.2021.777607 ◽

2021 ◽

Vol 12 ◽

Author(s):

Emine Eren-Koçak ◽

Turgay Dalkara

Keyword(s):

Ion Channels ◽

Ion Channel ◽

Energy Homeostasis ◽

Inflammatory Signaling ◽

Pannexin 1 ◽

Significant Heritability ◽

Homeostatic Function ◽

And Function ◽

Excitability Of Neurons

Migraine and major depression are debilitating disorders with high lifetime prevalence rates. Interestingly these disorders are highly comorbid and show significant heritability, suggesting shared pathophysiological mechanisms. Non-homeostatic function of ion channels and neuroinflammation may be common mechanisms underlying both disorders: The excitation-inhibition balance of microcircuits and their modulation by monoaminergic systems, which depend on the expression and function of membrane located K+, Na+, and Ca+2 channels, have been reported to be disturbed in both depression and migraine. Ion channels and energy supply to synapses not only change excitability of neurons but can also mediate the induction and maintenance of inflammatory signaling implicated in the pathophysiology of both disorders. In this respect, Pannexin-1 and P2X7 large-pore ion channel receptors can induce inflammasome formation that triggers release of pro-inflammatory mediators from the cell. Here, the role of ion channels involved in the regulation of excitation-inhibition balance, synaptic energy homeostasis as well as inflammatory signaling in migraine and depression will be reviewed.

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Decision letter: Regulation of food intake by mechanosensory ion channels in enteric neurons

10.7554/elife.04402.005 ◽

2014 ◽

Keyword(s):

Ion Channels ◽

Food Intake ◽

Enteric Neurons

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Faculty Opinions recommendation of Molecular genetic evidence that endometriosis is a precursor of ovarian cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.10321.472067 ◽

2006 ◽

Author(s):

Patrick Groothuis

Keyword(s):

Ovarian Cancer ◽

Molecular Genetic ◽

Genetic Evidence ◽

Molecular Genetic Evidence

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Central Histamine, the H3-Receptor and Obesity Therapy

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666190703094846 ◽

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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Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00358.2017 ◽

2018 ◽

Vol 315 (1) ◽

pp. E29-E37 ◽

Cited By ~ 3

Author(s):

Mariana Peduti Halah ◽

Paula Beatriz Marangon ◽

Jose Antunes-Rodrigues ◽

Lucila L. K. Elias

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Food Intake ◽

White Adipose Tissue ◽

Energy Homeostasis ◽

Body Weight Gain ◽

Adult Life ◽

Male Rats ◽

Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

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