scholarly journals A hindbrain dopaminergic neural circuit prevents weight gain by reinforcing food satiation

2021 ◽  
Vol 7 (22) ◽  
pp. eabf8719
Author(s):  
Yong Han ◽  
Guobin Xia ◽  
Yanlin He ◽  
Yang He ◽  
Monica Farias ◽  
...  
Keyword(s):  
Weight Gain ◽  
Food Intake ◽  
Neural Circuit ◽  
Neural Circuitry ◽  
Dynamic Regulation ◽  
Satiety Response ◽  
Food Satiation ◽  
Lateral Parabrachial Nucleus ◽  
Genetic Deletion ◽  
Feeding Bout

The neural circuitry mechanism that underlies dopaminergic (DA) control of innate feeding behavior is largely uncharacterized. Here, we identified a subpopulation of DA neurons situated in the caudal ventral tegmental area (cVTA) directly innervating DRD1-expressing neurons within the lateral parabrachial nucleus (LPBN). This neural circuit potently suppresses food intake via enhanced satiation response. Notably, this cohort of DAcVTA neurons is activated immediately before the cessation of each feeding bout. Acute inhibition of these DA neurons before bout termination substantially suppresses satiety and prolongs the consummatory feeding. Activation of postsynaptic DRD1LPBN neurons inhibits feeding, whereas genetic deletion of Drd1 within the LPBN causes robust increase in food intake and subsequent weight gain. Furthermore, the DRD1LPBN signaling manifests the central mechanism in methylphenidate-induced hypophagia. In conclusion, our study illuminates a hindbrain DAergic circuit that controls feeding through dynamic regulation in satiety response and meal structure.

Increased short-term food satiation and sensitivity to cholecystokinin in neurotrophin-4 knock-in mice

2004 ◽  
Vol 287 (5) ◽  
pp. R1044-R1053 ◽  
Author(s):  
Michael M. Chi ◽  
Guoping Fan ◽  
Edward A. Fox
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Knockout Mice ◽  
Meal Frequency ◽  
Short Term ◽  
Daily Food Intake ◽  
Food Satiation ◽  
Daily Food ◽  
Solid Diet

Neurotrophin-4 (NT-4) knockout mice exhibited decreased innervation of the small intestine by vagal intraganglionic laminar endings (IGLEs) and reduced food satiation. Recent findings suggested this innervation was increased in NT-4 knock-in (NT-4KI) mice. Therefore, to further investigate the relationship between intestinal IGLEs and satiation, meal patterns were characterized using solid and liquid diets, and cholecystokinin (CCK) effects on 30-min solid diet intake were examined in NT-4KI and wild-type mice. NT-4KI mice consuming the solid diet exhibited reduced meal size, suggesting increased satiation. However, compensation occurred through increased meal frequency, maintaining daily food intake and body weight gain similar to controls. Mutants fed the liquid diet displayed a decrease in intake rate, again implying increased satiation, but meal duration increased, which led to an increase in meal size. This was compensated for by decreased meal frequency, resulting in similar daily food intake and weight gain as controls. Importantly, these alterations in NT-4KI mice were opposite, or different, from those of NT-4 knockout mice, further supporting the hypothesis that they are specific to vagal afferent signaling. CCK suppressed short-term intake in mutants and controls, but the mutants exhibited larger suppressions at lower doses, implying they were more sensitive to CCK. Moreover, devazepide prevented this suppression, indicating this increased sensitivity was mediated by CCK-1 receptors. These results suggest that the NT-4 gene knock-in, probably involving increased intestinal IGLE innervation, altered short-term feeding, in particular by enhancing satiation and sensitivity to CCK, whereas long-term control of daily intake and body weight was unaffected.

scholarly journals Ghrelin in the lateral parabrachial nucleus influences the excitability of glucosensing neurons, increases food intake and body weight

2020 ◽  
Vol 9 (12) ◽  
pp. 1168-1177
Author(s):  
Caishun Zhang ◽  
Junhua Yuan ◽  
Qian Lin ◽  
Manwen Li ◽  
Liuxin Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Firing Rate ◽  
Body Weight Gain ◽  
Parabrachial Nucleus ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Lateral Parabrachial Nucleus

Ghrelin plays a pivotal role in the regulation of food intake, body weight and energy metabolism. However, these effects of ghrelin in the lateral parabrachial nucleus (LPBN) are unexplored. C57BL/6J mice and GHSR−/− mice were implanted with cannula above the right LPBN and ghrelin was microinjected via the cannula to investigate effect of ghrelin in the LPBN. In vivo electrophysiological technique was used to record LPBN glucose-sensitive neurons to explore potential udnderlying mechanisms. Microinjection of ghrelin in LPBN significantly increased food intake in the first 3 h, while such effect was blocked by [D-Lys3]-GHRP-6 and abolished in GHSR−/− mice. LPBN ghrelin microinjection also significantly increased the firing rate of glucose-excited (GE) neurons and decreased the firing rate of glucose-inhibited (GI) neurons. Additionally, LPBN ghrelin microinjection also significantly increased c-fos expression. Chronic ghrelin administration in the LPBN resulted in significantly increased body weight gain. Meanwhile, no significant changes were observed in both mRNA and protein expression levels of UCP-1 in BAT. These results demonstrated that microinjection of ghrelin in LPBN could increase food intake through the interaction with growth hormone secretagogue receptor (GHSR) in C57BL/6J mice, and its chronic administration could also increase body weight gain. These effects might be associated with altered firing rate in the GE and GI neurons.

scholarly journals Functional and Neurochemical Identification of Ghrelin Receptor (GHSR)-Expressing Cells of the Lateral Parabrachial Nucleus in Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Marie V. Le May ◽  
Fiona Peris-Sampedro ◽  
Iris Stoltenborg ◽  
Erik Schéle ◽  
Tina Bake ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Food Choice ◽  
Viral Vector ◽  
Sucrose Solution ◽  
Parabrachial Nucleus ◽  
Growth Hormone Secretagogue ◽  
Lateral Parabrachial Nucleus ◽  
Obesogenic Diet

The lateral parabrachial nucleus (lPBN), located in the pons, is a well-recognized anorexigenic center harboring, amongst others, the calcitonin gene-related peptide (CGRP)-expressing neurons that play a key role. The receptor for the orexigenic hormone ghrelin (the growth hormone secretagogue receptor, GHSR) is also abundantly expressed in the lPBN and ghrelin delivery to this site has recently been shown to increase food intake and alter food choice. Here we sought to explore whether GHSR-expressing cells in the lPBN (GHSRlPBN cells) contribute to feeding control, food choice and body weight gain in mice offered an obesogenic diet, involving studies in which GHSRlPBN cells were silenced. We also explored the neurochemical identity of GHSRlPBN cells. To silence GHSRlPBN cells, Ghsr-IRES-Cre male mice were bilaterally injected intra-lPBN with a Cre-dependent viral vector expressing tetanus toxin-light chain. Unlike control wild-type littermates that significantly increased in body weight on the obesogenic diet (i.e., high-fat high-sugar free choice diet comprising chow, lard and 9% sucrose solution), the heterozygous mice with silenced GHSRlPBN cells were resistant to diet-induced weight gain with significantly lower food intake and fat weight. The lean phenotype appeared to result from a decreased food intake compared to controls and caloric efficiency was unaltered. Additionally, silencing the GHSRlPBN cells altered food choice, significantly reducing palatable food consumption. RNAscope and immunohistochemical studies of the lPBN revealed considerable co-expression of GHSR with glutamate and pituitary adenylate cyclase-activating peptide (PACAP), and much less with neurotensin, substance P and CGRP. Thus, the GHSRlPBN cells are important for diet-induced weight gain and adiposity, as well as in the regulation of food intake and food choice. Most GHSRlPBN cells were found to be glutamatergic and the majority (76%) do not belong to the well-characterized anorexigenic CGRP cell population.

scholarly journals Role of Ventromedial Hypothalamus in Sucrose-Induced Obesity on Metabolic Parameters

2021 ◽  
pp. 097275312110057
Author(s):  
Archana Gaur ◽  
G.K. Pal ◽  
Pravati Pal
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Food Intake ◽  
Ventromedial Hypothalamus ◽  
Female Rats ◽  
Metabolic Parameters ◽  
Male Rats ◽  
Significant Weight Gain ◽  
The Metabolic Syndrome

Background: Obesity is because of excessive fat accumulation that affects health adversely in the form of various diseases such as diabetes, hypertension, cardiovascular diseases, and many other disorders. Our Indian diet is rich in carbohydrates, and hence the sucrose-induced obesity is an apt model to mimic this. Ventromedial hypothalamus (VMH) is linked to the regulation of food intake in animals as well as humans. Purpose: To understand the role of VMHin sucrose-induced obesity on metabolic parameters. Methods: A total of 24 adult rats were made obese by feeding them on a 32% sucrose solution for 10 weeks. The VMH nucleus was ablated in the experimental group and sham lesions were made in the control group. Food intake, body weight, and biochemical parameters were compared before and after the lesion. Results: Male rats had a significant weight gain along with hyperphagia, whereas female rats did not have a significant weight gain inspite of hyperphagia. Insulin resistance and dyslipidemia were seen in both the experimental and control groups. Conclusion: A sucrose diet produces obesity which is similar to the metabolic syndrome with insulin resistance and dyslipidemia, and a VMH lesion further exaggerates it. Males are more prone to this exaggeration.

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

2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
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.

Phenobarbital Effects on Weight Gain and Circadian Cycling of Food Intake and Body Temperature

1980 ◽  
Vol 165 (3) ◽  
pp. 473-479 ◽  
Author(s):  
C. Peraino ◽  
C. F. Ehret ◽  
K. R. Groh ◽  
J. C. Meinert ◽  
G. D'Arcy-Gomez
Keyword(s):  
Weight Gain ◽  
Food Intake ◽  
Body Temperature

A comparison of the effects of infection with Eimeria maxima and dietary restriction on weight gain, plasma metabolites and liver glycogen in the immature fowl, Gallus domesticus

Parasitology ◽  
1982 ◽  
Vol 84 (2) ◽  
pp. 205-213 ◽  
Author(s):  
H. D. Chapman ◽  
D. L. Fernandes ◽  
T. F. Davison
Keyword(s):  
Growth Rate ◽  
Body Weight ◽  
Uric Acid ◽  
Weight Gain ◽  
Food Intake ◽  
Acute Phase ◽  
Plasma Glucose ◽  
Liver Glycogen ◽  
Plasma Metabolites ◽  
Eimeria Maxima

SUMMARYThe effects of Eimeria maxima or restricted pair-feeding on weight gain, plasma concentrations of protein, glucose, free fatty acids (FFA) and uric acid and liver glycogen were compared in immature fowl. Food intake/kg body weight and weight gain decreased during the acute phase of infection (days 5–7) while weight loss was prolonged for an extra day compared with pair-fed birds. During recovery, food intake/kg body weight of infected birds was greater than that of non-infected controls but there was no evidence for an increase in growth rate compared with controls when body weight was considered. Growth rate of pair-fed birds was greater than that of infected birds during recovery, indicating their better use of ingested food. Liver glycogen and plasma protein concentration were decreased during the acute phase of infection but the concentrations of plasma glucose, free fatty acid (FFA) and uric acid were not affected. In pair-fed birds liver glycogen was depleted, concentrations of plasma glucose and uric acid decreased and FFA increased, and these changes persisted for the remainder of the experiment. The findings are similar to those in birds whose food has been withheld and were probably due to the pattern of food intake imposed by the experimental protocol. It is concluded that the metabolic differences between infected and pair-fed birds are of doubtful significance.

Intestinal motility during acute Yersinia enterocolitica enteritis in rabbits

1989 ◽  
Vol 67 (6) ◽  
pp. 553-560 ◽  
Author(s):  
R. B. Scott ◽  
D. G. Gall ◽  
S. C. Diamant
Keyword(s):  
Weight Gain ◽  
Food Intake ◽  
Motor Activity ◽  
Yersinia Enterocolitica ◽  
Phase Iii ◽  
Intestinal Lumen ◽  
Fecal Excretion ◽  
Cycle Period ◽  
Motility Index ◽  
And Control

To determine if Yersinia enterocolitica (YE) enteritis is associated with an alteration of intestinal myoelectric and motor activity, and with an increased rate of aboral transit, New Zealand white rabbits (500–900 g) were surgically prepared with ileal bipolar electrodes and a manometry catheter adjacent to the distal electrode. One week later animals were inoculated with 1010 organisms of YE in 10 mL NaHCO3 (infected group) or 10 mL NaHCO3 (sham-infected pair-fed and control groups). Daily food intake, weight gain, YE excretion, and stool pattern were noted. Intestinal myoelectric and motor activity over a 6- to 8- h period before and 3, 6, and 14 days after inoculation was compared in infected (I), pair-fed (PF), and control (C) groups. Intestinal transit was evaluated in I and C animals on days 3 and 6 after inoculation by measuring the distribution in the intestinal lumen of 51Cr 20 min after it was instilled directly into the jejunum. Infected animals exhibited diarrhea, fecal excretion of YE, and significantly decreased food intake, weight gain, and survival (11.4 ± 0.6 days). Infection was associated with a significant (p < 0.05) decrease in both the cycle period of the migrating myoelectric complex (MMC) and the total number of single, paired, and (or) clustered contractions per MMC, and a significant (p < 0.001) increase in duration of phase III of the MMC. There was no change in intestinal slow wave frequency (19 cycles/min), motility index per MMC, or the percentage of contractions that propagated in an orad (7%) or aboral (69%) direction or that appeared stationary (25%). The changes in myoelectric and motor activity were specific for YE infection (not related to decreased food intake and weight gain) and were associated with a significantly increased rate of aboral transit. Thus, the inflammatory enteritis induced by YE is associated with alterations of intestinal myoelectric and motor activity, and an increased rate of aboral transit.Key words: Yersinia enterocolitica, infection, intestine, motility, transit.

scholarly journals The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2441-2452 ◽  
Author(s):  
Tomokazu Hata ◽  
Noriyuki Miyata ◽  
Shu Takakura ◽  
Kazufumi Yoshihara ◽  
Yasunari Asano ◽  
...  
Keyword(s):  
Body Weight ◽  
Anorexia Nervosa ◽  
Weight Gain ◽  
Food Intake ◽  
Brain Stem ◽  
Body Weight Gain ◽  
Field Tests ◽  
Compulsive Behavior ◽  
The Brain ◽  
Poor Weight Gain

Abstract Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.

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