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.

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 5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding

2021 ◽  
Author(s):  
Yanlin He ◽  
Xing Cai ◽  
Hailan Liu ◽  
Krisitine M. Conde ◽  
Pingwen Xu ◽  
...  
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Ventral Tegmental Area ◽  
Arcuate Nucleus ◽  
Outward Current ◽  
Raphe Nucleus ◽  
Area 5 ◽  
Parallel Circuits ◽  
Different Types ◽  
Hypothalamic Arcuate Nucleus

AbstractObesity is primarily a consequence of consuming calories beyond energetic requirements, but underpinning drivers have not been fully defined. 5-Hydroxytryptamine (5-HT) neurons in the dorsal Raphe nucleus (5-HTDRN) regulate different types of feeding behavior, such as eating to cope with hunger or for pleasure. Here, we observed that activation of 5-HTDRN to hypothalamic arcuate nucleus (5-HTDRN → ARH) projections inhibits food intake driven by hunger via actions at ARH 5-HT2C and 5-HT1B receptors, whereas activation of 5-HTDRN to ventral tegmental area (5-HTDRN → VTA) projections inhibits non-hunger-driven feeding via actions at 5-HT2C receptors. Further, hunger-driven feeding gradually activates ARH-projecting 5-HTDRN neurons via inhibiting their responsiveness to inhibitory GABAergic inputs; non-hunger-driven feeding activates VTA-projecting 5-HTDRN neurons through reducing a potassium outward current. Thus, our results support a model whereby parallel circuits modulate feeding behavior either in response to hunger or to hunger-independent cues.

scholarly journals Energy Status Differentially Modifies Feeding Behavior and POMCARC Neuron Activity After Acute Treadmill Exercise in Untrained Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Taylor Landry ◽  
Daniel Shookster ◽  
Alec Chaves ◽  
Katrina Free ◽  
Tony Nguyen ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Food Intake ◽  
Feeding Behavior ◽  
Exercise Intensity ◽  
High Intensity ◽  
Treadmill Exercise ◽  
High Intensity Exercise ◽  
Neuron Activity ◽  
Energy Status ◽  
Post Exercise

Emerging evidence identifies a potent role for aerobic exercise to modulate activity of neurons involved in regulating appetite; however, these studies produce conflicting results. These discrepancies may be, in part, due to methodological differences, including differences in exercise intensity and pre-exercise energy status. Consequently, the current study utilized a translational, well-controlled, within-subject, treadmill exercise protocol to investigate the differential effects of energy status and exercise intensity on post-exercise feeding behavior and appetite-controlling neurons in the hypothalamus. Mature, untrained male mice were exposed to acute sedentary, low (10m/min), moderate (14m/min), and high (18m/min) intensity treadmill exercise in a randomized crossover design. Fed and 10-hour-fasted mice were used, and food intake was monitored 48h. post-exercise. Immunohistochemical detection of cFOS was performed 1-hour post-exercise to determine changes in hypothalamic NPY/AgRP, POMC, tyrosine hydroxylase, and SIM1-expressing neuron activity concurrent with changes in food intake. Additionally, stains for pSTAT3tyr705 and pERKthr202/tyr204 were performed to detect exercise-mediated changes in intracellular signaling. Results demonstrated that fasted high intensity exercise suppressed food intake compared to sedentary trials, which was concurrent with increased anorexigenic POMC neuron activity. Conversely, fed mice experienced augmented post-exercise food intake, with no effects on POMC neuron activity. Regardless of pre-exercise energy status, tyrosine hydroxylase and SIM1 neuron activity in the paraventricular nucleus was elevated, as well as NPY/AgRP neuron activity in the arcuate nucleus. Notably, these neuronal changes were independent from changes in pSTAT3tyr705 and pERKthr202/tyr204 signaling. Overall, these results suggest fasted high intensity exercise may be beneficial for suppressing food intake, possibly due to hypothalamic POMC neuron excitation. Furthermore, this study identifies a novel role for pre-exercise energy status to differentially modify post-exercise feeding behavior and hypothalamic neuron activity, which may explain the inconsistent results from studies investigating exercise as a weight loss intervention.

scholarly journals A temperature-regulated circuit for feeding behavior

2021 ◽  
Author(s):  
Shaowen Qian ◽  
Sumei Yan ◽  
Ruiqi Pang ◽  
Jing Zhang ◽  
Kai Liu ◽  
...  
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Arcuate Nucleus ◽  
Preoptic Area ◽  
Hypothalamic Nucleus ◽  
Galanin Receptor ◽  
Neuronal Populations ◽  
Lateral Parabrachial Nucleus ◽  
Apelin Receptor ◽  
Feeding Center

Abstract Both rodents and primates have evolved to orchestrate food intake to maintain thermal homeostasis in coping with ambient temperature challenges. However, the mechanisms underlying temperature-coordinated feeding behavior are rarely reported. Here we found that a non-canonical feeding center, the anteroventral and periventricular portions of medial preoptic area (apMPOA) responded to altered dietary states. Two neighboring but distinct apMPOA neurons mediated feeding in receiving anatomical inputs from external and dorsal subnuclei of lateral parabrachial nucleus (LPB). While both populations are glutamatergic, the arcuate nucleus (ARC)-projecting neurons in apMPOA can sense low temperature and promote food intake. The other type, the paraventricular hypothalamic nucleus (PVH)-projecting neurons in apMPOA are primarily sensitive to high temperature and suppress food intake. Cutting off both pathways can eliminate the temperature-dependence of feeding. Further projection-specific RNA sequencing identified that the two neuronal populations were molecularly marked by galanin receptor and apelin receptor. These findings reveal an unrecognized cell populations and circuits of apMPOA that orchestrates feeding behavior against thermal challenges.

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.

Agouti-related protein increases food hoarding more than food intake in Siberian hamsters

2004 ◽  
Vol 286 (1) ◽  
pp. R38-R45 ◽  
Author(s):  
Diane E. Day ◽  
Timothy J. Bartness
Keyword(s):  
Food Intake ◽  
Arcuate Nucleus ◽  
Third Ventricle ◽  
Mass Gain ◽  
Dark Phase ◽  
Related Protein ◽  
Food Hoarding ◽  
Laboratory Rats ◽  
Siberian Hamsters ◽  
Agouti Related Protein

Agouti-related protein (AgRP), an endogenous melanocortin 3/4 receptor antagonist, appears to play an important role in the control of food intake and energy balance because exogenous administration in rats and overexpression in mice result in hyperphagia and body mass gain. Furthermore, arcuate nucleus AgRP mRNA is increased with fasting in laboratory rats and mice and is decreased with refeeding. In Siberian hamsters, fasting also increases arcuate nucleus AgRP mRNA, but these animals increase food hoarding, rather than food intake with refeeding. Therefore, we tested whether exogenous AgRP increased food hoarding in this species. Hamsters were trained in a hoarding/foraging apparatus to run a programmed number of wheel revolutions to earn food pellets. Four doses of AgRP-(83-132) or vehicle were injected into the third ventricle at the beginning of the dark phase, and food hoarding, food intake, and foraging were measured at various time points subsequently. Overall, food hoarding was stimulated as much as 10 times more than food intake, and both responses occurred as early as 1 h after injection. Food hoarding was increased the greatest at the lowest dose (0.1 nmol), whereas food intake was increased the greatest at the second lowest dose (1 nmol). Food intake and especially food hoarding were increased up to seven days after the AgRP injections. Foraging was increased at all AgRP doses except the highest dose (100 nmol). These results suggest that AgRP triggers the search for food in this species, and once they find it, hoarding predominates over eating.

Metabolic inhibitors synergistically decrease hepatic energy status and increase food intake

2000 ◽  
Vol 278 (6) ◽  
pp. R1579-R1582 ◽  
Author(s):  
Hong Ji ◽  
Grazyna Graczyk-Milbrandt ◽  
Mark I. Friedman
Keyword(s):  
Food Intake ◽  
Synergistic Effect ◽  
Feeding Behavior ◽  
Combined Treatment ◽  
Metabolic Inhibitors ◽  
Metabolic Inhibitor ◽  
Atp Content ◽  
Energy Status ◽  
Increase Food Intake ◽  
The Common

Previous studies indicate that administration of the metabolic inhibitor, 2,5-anhydro-d-mannitol (2,5-AM) or methyl palmoxirate (MP), induces feeding behavior in rats by lowering hepatic energy status. Combined treatment with these agents synergistically increases food intake. The present study was designed to investigate whether combined treatment also has a synergistic effect on hepatic energy status. Rats treated with both inhibitors increased feeding behavior compared with the controls, whereas those treated with 2,5-AM or MP alone did not. Although 2,5-AM alone lowered hepatic ATP content regardless of MP treatment, only the combination resulted in decreases in hepatic ATP/ADP ratio and phosphorylation potential. MP treatment did not affect the uptake of 2,5-AM into liver. These results suggest that a reduction in hepatic energy status is the common triggering signal for eating behavior induced by 2,5-AM and MP and provide additional evidence for an integrated metabolic control of food intake.

Effects of neurosecretory protein GL on food intake and fat accumulation under different dietary nutrient compositions in rats

2021 ◽  
Author(s):  
Keisuke Fukumura ◽  
Kenshiro Shikano ◽  
Yuaki Narimatsu ◽  
Eiko Iwakoshi-Ukena ◽  
Megumi Furumitsu ◽  
...  
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Body Mass ◽  
Mass Gain ◽  
Chow Diet ◽  
Tissue Mass ◽  
Fat Accumulation ◽  
Intracerebroventricular Infusion ◽  
Body Mass Gain ◽  
Sucrose Diet

Abstract We recently identified a novel hypothalamic small protein, named neurosecretory protein GL (NPGL), which is involved in energy homeostasis in birds and mammals. However, whether the action of NPGL is influenced by nutritional composition remains unknown. Thus, we investigated the effect of chronic intracerebroventricular infusion of NPGL for 13 days on feeding behavior and body mass gain under a normal chow diet (NC), high-fat diet, high-sucrose diet (HSD), and medium-fat/medium-sucrose diet (MFSD) in rats. NPGL stimulated food intake of NC and MFSD, especially during the light period. By contrast, NPGL decreased body mass gain under NC and increased total white adipose tissue mass in HSD- and MFSD-fed rats. These data suggest that the effects of NPGL on feeding behavior, body mass gain, and fat accumulation depend on nutrient type. Among them, sucrose in diets seems to contribute to fat accumulation elicited by NPGL.

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