scholarly journals Role of Neuronal Energy Status in the Regulation of Adenosine 5′-Monophosphate-Activated Protein Kinase, Orexigenic Neuropeptides Expression, and Feeding Behavior

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Kichoon Lee ◽  
Bing Li ◽  
Xiaochun Xi ◽  
Yeunsu Suh ◽  
Roy J. Martin
Keyword(s):  
Protein Kinase ◽  
Food Intake ◽  
Feeding Behavior ◽  
High Glucose ◽  
Ex Vivo ◽  
Nutrient Sensing ◽  
Central Administration ◽  
Energy Status ◽  
Low Glucose

Nutrient sensing in the hypothalamus is tightly related to food intake regulation. However, the mechanisms by which the nutrient-sensing cells of the brain translate this signal of energy need into feeding behavior via regulation of neuropeptide expression are not known. To address this issue, we investigated two neuronal cell lines expressing agouti-related protein (AgRP), ex vivo hypothalamic tissues, and in vivo whole animals. Maintaining cells in a low cellular ATP concentration generated by low glucose, 2-deoxyglucose (2-DG), ATP synthesis inhibitor, and 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside increased phosphorylation of AMP-activated protein kinase (AMPK) and increased AgRP expression, whereas maintaining cells in high ATP status by high glucose and pyruvate supplementation in 2-DG-treated cells decreased phosphorylation of AMPK and decreased AgRP expression. Overexpression of a dominant-inhibitory mutant of AMPK significantly decreased low-glucose- or 2-DG-induced AgRP expression. Furthermore, ex vivo hypothalamus culture in high glucose concentrations decreased both expression and phosphorylation of AMPK and expression of both AgRP and neuropeptide Y, whereas pyruvate supplementation suppressed a 2-DG-induced AgRP expression. Finally, our in vivo studies clearly show that central administration of pyruvate dramatically delayed 2-DG-induced food intake. These data indicate that modulation of ATP levels in neuronal cells triggers a cascade of events via AMPK that modulate feeding behavior to restore energy status of cells.

Fatty acid oxidation affects food intake by altering hepatic energy status

1999 ◽  
Vol 276 (4) ◽  
pp. R1046-R1053 ◽  
Author(s):  
Mark I. Friedman ◽  
Ruth B. Harris ◽  
Hong Ji ◽  
Israel Ramirez ◽  
Michael G. Tordoff
Keyword(s):  
Fatty Acid ◽  
Food Intake ◽  
Feeding Behavior ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Energy Status ◽  
Hepatic Fatty Acid ◽  
Hepatic Fatty Acid Oxidation

Inhibition of fatty acid oxidation stimulates feeding behavior in rats. To determine whether a decrease in hepatic fatty acid oxidation triggers this behavioral response, we compared the effects of different doses of methyl palmoxirate (MP), an inhibitor of fatty acid oxidation, on food intake with those on in vivo and in vitro liver and muscle metabolism. Administration of 1 mg/kg MP selectively decreased hepatic fatty acid oxidation but did not stimulate food intake. In contrast, feeding behavior increased in rats given 5 or 10 mg/kg MP, which inhibited hepatic fatty acid oxidation to the same extent as did the low dose but in addition suppressed fatty acid oxidation in muscle and produced a marked depletion of liver glycogen. Dose-related increases in food intake tracked dose-related reductions in liver ATP content, ATP-to-ADP ratio, and phosphorylation potential. The findings suggest that a decrease in hepatic fatty acid oxidation can stimulate feeding behavior by reducing hepatic energy production.

scholarly journals The pathophysiologic role of the protein kinase Cδ pathway in the intervertebral discs of rabbits and mice: In vitro, ex vivo, and in vivo studies

2012 ◽  
Vol 64 (6) ◽  
pp. 1950-1959 ◽  
Author(s):  
Michael B. Ellman ◽  
Jae-Sung Kim ◽  
Howard S. An ◽  
Jeffrey S. Kroin ◽  
Xin Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ex Vivo ◽  
Intervertebral Discs ◽  
In Vivo Studies ◽  
Protein Kinase Cδ

scholarly journals Baicalin suppresses lung cancer growth by targeting PDZ-binding kinase/T-LAK cell-originated protein kinase

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Xin Diao ◽  
Danfen Yang ◽  
Yu Chen ◽  
Wentian Liu
Keyword(s):  
Lung Cancer ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Ex Vivo ◽  
Lung Cancer Cells ◽  
Cancer Growth ◽  
Downstream Signaling ◽  
Lak Cell

AbstractBaicalin is the main bioactive component extracted from the traditional Chinese medicine Baical Skullcap Root, and its anti-tumor activity has been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in many cancer cells and stimulates the tumorigenic properties, and so, it is a pivotal target for agent to cure cancers. We reported for the first time that baicalin suppressed PBK/TOPK activities by directly binding with PBK/TOPK in vitro and in vivo. Ex vivo studies showed that baicalin suppressed PBK/TOPK activity in JB6 Cl41 cells and H441 lung cancer cells. Moreover, knockdown of PBK/TOPK in H441 cells decreased their sensitivity to baicalin. In vivo study indicated that injection of baicalin in H441 tumor-bearing mice effectively suppressed cancer growth. The PBK/TOPK downstream signaling molecules Histone H3 and ERK2 in tumor tissues were also decreased after baicalin treatment. Taken together, baicalin can inhibit proliferation of lung cancer cells as a PBK/TOPK inhibitor both in vitro and in vivo.

scholarly journals Nutrient-sensing mTOR-mediated pathway regulates leptin production in isolated rat adipocytes

2003 ◽  
Vol 284 (2) ◽  
pp. E322-E330 ◽  
Author(s):  
Cecilia Roh ◽  
Jianrong Han ◽  
Alexandros Tzatsos ◽  
Konstantin V. Kandror
Keyword(s):  
Endoplasmic Reticulum ◽  
Food Intake ◽  
Mammalian Target Of Rapamycin ◽  
Heavy Fraction ◽  
Nutrient Sensing ◽  
Rat Adipocytes ◽  
Cytosolic Extract ◽  
Adipose Cells ◽  
Isolated Rat

Leptin biosynthesis in adipose cells in vivo is increased by food intake and decreased by food deprivation. However, the mechanism that couples leptin production to food intake remains unknown. We found that addition of leucine to isolated rat adipocytes significantly increased leptin production by these cells, suggesting that postprandial leptin levels may be directly regulated by dietary leucine. The effect of leucine was inhibited by rapamycin and not by actinomycin D. Besides, leucine administration did not increase the amount of leptin mRNA in adipocytes. Therefore, we concluded that leucine activates leptin expression in adipose cells at the level of translation via a mammalian target of rapamycin (mTOR)-mediated pathway. Because leptin is a secreted protein, its biosynthesis is compartmentalized on the endoplasmic reticulum. To analyze mTOR signaling in this subcellular fraction, we separated adipose cells by centrifugation into a heavy membrane fraction that includes virtually all endoplasmic reticulum and the cytosolic extract. Phosphorylation of the major mTOR targets, the ribosomal protein S6 and the translational inhibitor 4E-binding protein (BP)/phosphorylated heat- and acid-stable protein (PHAS)-1, was stimulated by leucine in the cytosolic extract, whereas, in the heavy fraction, S6 was constitutively phosphorylated and leucine only induced phosphorylation of 4E-BP/PHAS-1. We also found that 60–70% of leptin mRNA was stably associated with the heavy fraction, and leucine administration did not change the ratio between compartmentalized and free cytoplasmic leptin mRNA. We suggest that, in adipose cells, a predominant part of leptin mRNA is compartmentalized on the endoplasmic reticulum, and leucine activates translation of these messages via the mTOR/4E-BP/PHAS-1-mediated signaling pathway.

scholarly journals Integration of Nutrient Sensing in Fish Hypothalamus

2021 ◽  
Vol 15 ◽  
Author(s):  
José L. Soengas
Keyword(s):  
Protein Kinase ◽  
Food Intake ◽  
Camp Response Element Binding ◽  
Nutrient Sensing ◽  
Future Research ◽  
Camp Response Element ◽  
Element Binding Protein ◽  
Homeobox Transcription Factor ◽  
Endocrine Signaling ◽  
Amp Activated Protein Kinase

The knowledge regarding hypothalamic integration of metabolic and endocrine signaling resulting in regulation of food intake is scarce in fish. Available studies pointed to a network in which the activation of the nutrient-sensing (glucose, fatty acid, and amino acid) systems would result in AMP-activated protein kinase (AMPK) inhibition and activation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Changes in these signaling pathways would control phosphorylation of transcription factors cAMP response-element binding protein (CREB), forkhead box01 (FoxO1), and brain homeobox transcription factor (BSX) leading to food intake inhibition through changes in the expression of neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opio melanocortin (POMC), and cocaine and amphetamine-related transcript (CART). The present mini-review summarizes information on the topic and identifies gaps for future research.

scholarly journals Astrocytes in the dorsal vagal complex are not activated by systemic glucoprivation and their chemogenetic activation does not elicit homeostatic glucoregulatory responses in mice

2021 ◽  
Author(s):  
Alastair J MacDonald ◽  
Katherine R Pye ◽  
Craig Beall ◽  
Kate LJ Ellacott
Keyword(s):  
Blood Glucose ◽  
Food Intake ◽  
Ex Vivo ◽  
Glucose Deprivation ◽  
Active Role ◽  
Glucose Absorption ◽  
Dorsal Vagal Complex ◽  
Gfap Immunoreactivity ◽  
Regulate Food Intake

The dorsal vagal complex (DVC) is a brainstem site regulating diverse aspects of physiology including food intake and blood glucose homeostasis. Astrocytes are purported to play an active role in regulating DVC function and, by extension, physiological parameters. Previous work has demonstrated that DVC astrocytes directly sense hormones that regulate food intake and blood glucose and are critical for their effect. In addition, DVC astrocytes in ex vivo slices respond to low tissue glucose. The response of neurons, including catecholaminergic neurons, to low glucose is conditional on intact astrocyte signalling in slice preparations suggesting astrocytes are possibly the primary sensors of glucose deprivation (glucoprivation). Based on these findings we hypothesised that if DVC astrocytes act as glucoprivation sensors in vivo they would both show a response to systemic glucoprivation and drive physiological responses to restore blood glucose. We found that 2 hours of systemic glucoprivation induced neither FOS nor glial fibrillary acidic protein (GFAP)-immunoreactivity in DVC astrocytes, specifically those in the nucleus of the solitary tract (NTS). Furthermore, we found that while chemogenetic activation of DVC astrocytes suppressed food intake by reducing both meal size and meal number, this manipulation also suppressed food intake under conditions of glucoprivation. Chemogenetic activation of DVC astrocytes did not increase basal blood glucose nor protect against insulin-induced hypoglycaemia. In male mice chemogenetic DVC astrocyte activation did not alter glucose tolerance, in female mice the initial glucose excursion was reduced, suggesting enhanced glucose absorption. Taken together this suggests that as a whole-population DVC astrocytes do not function as glucoprivation sensors in vivo in mice. Instead, we propose that DVC astrocytes play an indispensable, homeostatic role to maintain the function of glucoregulatory neuronal circuitry.

Glucagon-like peptide 1-(7–36) amide acts at lateral and medial hypothalamic sites to suppress feeding in rats

2003 ◽  
Vol 284 (6) ◽  
pp. R1427-R1435 ◽  
Author(s):  
Rafael R. Schick ◽  
Jens P. Zimmermann ◽  
Thomas vorm Walde ◽  
Volker Schusdziarra
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Effective Dose ◽  
Ventromedial Hypothalamus ◽  
Brain Regions ◽  
Central Administration ◽  
Minimal Effective Dose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Fasted Rats

Glucagon-like peptide 1-(7–36) amide (GLP-1) potently inhibits rat feeding behavior after central administration. Because third ventricular injection of GLP-1 appeared to be less effective than lateral ventricular injection, we have reexamined this issue. In addition, we attempted to identify brain regions other than the paraventricular nucleus of the hypothalamus that are sensitive toward GLP-1-induced feeding suppression. Finally, we examined the local role of endogenous GLP-1 by specific GLP-1 receptor blockade. After lateral ventricular injection, GLP-1 significantly inhibited food intake of 24-h-fasted rats in a dose-dependent fashion with a minimal effective dose of 1 μg. After third ventricular injection, GLP-1 (1 μg) was similarly effective in suppressing food intake, which extends previous findings. Intracerebral microinjections of GLP-1 significantly suppressed food intake in the lateral (LH), dorsomedial (DMH), and ventromedial hypothalamus (VMH), but not in the medial nucleus of the amygdala. The minimal effective dose of GLP-1 was 0.3 μg at LH sites and 1 μg at DMH or VMH sites. LH microinjections of exendin-(9–39) amide, a GLP-1 receptor antagonist, at 1 or 2.5 μg did not alter feeding behavior in 24-h-fasted rats. In satiated animals, however, a single LH injection of 1 μg exendin-(9–39) amide significantly augmented food intake, but only during the first 20 min (0.6 vs. 0.1 g). With three repeated injections of 2.5 μg exendin-(9–39) amide every 20 min, 1-h food intake was significantly increased by 300%. These data strongly support and extend the concept of GLP-1 as a physiological regulator of food intake in the hypothalamus.

scholarly journals Endogenous Nitric Oxide and Dopamine Regulate Feeding Behavior in Neonatal Layer-type Chickens

2017 ◽  
Vol 17 (4) ◽  
pp. 1029-1042 ◽  
Author(s):  
Morteza Zendehdel ◽  
Yasaman Moosadoost ◽  
Reza Masoumi ◽  
Behnam Rostami ◽  
Mohammad Hossein Shahir ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Food Intake ◽  
Feeding Behavior ◽  
Animal Studies ◽  
Central Administration ◽  
Nitric Oxide Synthase Inhibitor ◽  
Endogenous Nitric Oxide ◽  
Food Intake Regulation ◽  
Synthase Inhibitor ◽  
Intake Regulation

AbstractEvidence from animal studies suggests that endogenous nitric oxide and dopamine (DA) have a regulatory role in the rewarding system, but their interaction(s) have not been studied in avian species. In this study, 4 experiments were performed to determine the effects of central administration of L-arginine (nitric oxide precursor; 200 nmol), NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor; 100 nmol), amphetamine (an indirect DA agonist; 125 pmol) and DA (40 pmol) on feeding behavior in neonatal layer-type chickens (each experiment included 4 groups, n=12 birds in each group). Prior to the initiation of the treatments, birds were fasted for 3 hours (FD3). In experiment 1, chickens received intracerebroventricular (ICV) injection of saline, L-NAME (100 nmol), amphetamine (125 pmol), and combination of L-NAME + amphetamine. In experiment 2, chickens received the ICV injection of saline, L-arginine (200 nmol), amphetamine (125 pmol) and their combination. In experiment 3, chickens received ICV injection of saline, L-arginine (200 nmol), DA (40 pmol) and L-arginine + DA. In experiment 4, chickens received ICV injection of saline, L-NAME (100 nmol), DA (40 pmol) and L-NAME + DA. Thereafter, the cumulative food intake (on the basis of metabolic body weight) was recorded until 2-h post injection. The results showed that ICV injection of amphetamine or DA significantly decreased food intake (P<0.05). Also, co-administration of L-NAME + amphetamine attenuated the hypophagic effect of amphetamine (P<0.05), while combined administration of L-NAME and DA had no effect on DA-induced hypophagia. Additionally, the hypophagic effect of amphetamine was significantly amplified by L-arginine (P<0.05), but the combination of L-arginine and DA did not alter feeding behavior which was induced by DA. These results suggest an interaction between DAergic and nitrergic systems via a presynaptic mechanism on food intake regulation in layer-type chicken.

scholarly journals Inhibition of Hypothalamic MCT4 and MCT1–MCT4 Expressions Affects Food Intake and Alters Orexigenic and Anorexigenic Neuropeptide Expressions

2019 ◽  
Vol 57 (2) ◽  
pp. 896-909 ◽  
Author(s):  
Roberto Elizondo-Vega ◽  
Karina Oyarce ◽  
Magdiel Salgado ◽  
María José Barahona ◽  
Antonia Recabal ◽  
...  
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Arcuate Nucleus ◽  
Third Ventricle ◽  
Monocarboxylate Transporters ◽  
Energy Status ◽  
Eating Rate ◽  
Behavior Regulation ◽  
Cellular Processes ◽  
Complex Process

Abstract Feeding behavior regulation is a complex process, which depends on the central integration of different signals, such as glucose, leptin, and ghrelin. Recent studies have shown that glial cells known as tanycytes that border the basal third ventricle (3V) detect glucose and then use glucose-derived signaling to inform energy status to arcuate nucleus (ARC) neurons to regulate feeding behavior. Monocarboxylate transporters (MCT) 1 and MCT4 are localized in the cellular processes of tanycytes, which could facilitate monocarboxylate release to orexigenic and anorexigenic neurons. We hypothesize that MCT1 and MCT4 inhibitions could alter the metabolic communication between tanycytes and ARC neurons, affecting feeding behavior. We have previously shown that MCT1 knockdown rats eat more and exhibit altered satiety parameters. Here, we generate MCT4 knockdown rats and MCT1–MCT4 double knockdown rats using adenovirus-mediated transduction of a shRNA into the 3V. Feeding behavior was evaluated in MCT4 and double knockdown animals, and neuropeptide expression in response to intracerebroventricular glucose administration was measured. MCT4 inhibition produced a decrease in food intake, contrary to double knockdown. MCT4 inhibition was accompanied by a decrease in eating rate and mean meal size and an increase in mean meal duration, parameters that are not changed in the double knockdown animals with exception of eating rate. Finally, we observed a loss in glucose regulation of orexigenic neuropeptides and abnormal expression of anorexigenic neuropeptides in response to fasting when these transporters are inhibited. Taken together, these results indicate that MCT1 and MCT4 expressions in tanycytes play a role in feeding behavior regulation.

scholarly journals Roles of 5′-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis

2003 ◽  
Vol 375 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Guy A. RUTTER ◽  
Gabriela da SILVA XAVIER ◽  
Isabelle LECLERC
Keyword(s):  
Protein Kinase ◽  
Glucose Production ◽  
Nutrient Sensing ◽  
Energy Status ◽  
Β Cells ◽  
Glucose Homoeostasis ◽  
New Findings ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
The Brain

AMPK (5′-AMP-activated protein kinase) is emerging as a metabolic master switch, by which cells in both mammals and lower organisms sense and decode changes in energy status. Changes in AMPK activity have been shown to regulate glucose transport in muscle and glucose production by the liver. Moreover, AMPK appears to be a key regulator of at least one transcription factor linked to a monogenic form of diabetes mellitus. As a result, considerable efforts are now under way to explore the usefulness of AMPK as a therapeutic target for other forms of this disease. Here we review this topic, and discuss new findings which suggest that AMPK may play roles in regulating insulin release and the survival of pancreatic islet β-cells, and nutrient sensing by the brain.

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