The actions of ghrelin in the paraventricular nucleus: energy balance and neuroendocrine implications

Dos‐Santos, Raoni Conceição; Reis, L. C.; Perelló, Mario; Ferguson, Alastair V.; Mecawi, André Souza

doi:10.1111/nyas.14087

Cited by 18 publications

(14 citation statements)

References 170 publications

(291 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, we found that AgRP‐Cre;Ghsr f/f mice under CR exhibited an increased fuel preference for carbohydrates, as well as a delayed switch to fatty acid metabolism after ingestion of scheduled meal in the dark phase. This contradicts the well‐accepted effect of centrally‐delivered ghrelin with respect to increasing RER and adiposity . On the other hand, the increase in RER in AgRP‐cre;Ghsr f/f mice is in line with our previous study showing that deletion of GHS‐R in all forebrain neurones ( Syn1‐cre;Ghsr f/f mice) increased RER, although it decreased body weight and percentage of fat in chow‐fed Syn1‐cre;Ghsr f/f mice .…”

Section: Discussioncontrasting

confidence: 49%

Ghrelin receptor in agouti‐related peptide neurones regulates metabolic adaptation to calorie restriction

Bongmba

Lee

et al. 2019

J Neuroendocrinology

View full text Add to dashboard Cite

Ghrelin is a gut hormone that signals to the hypothalamus to stimulate growth hormone release, increase food intake and promote fat deposition. The ghrelin receptor, also known as growth hormone secretagogue receptor (GHS‐R), is highly expressed in the brain, with the highest expression in agouti‐related peptide (AgRP) neurones in the hypothalamus. Compelling evidence indicates that ghrelin serves as a survival hormone with respect to maintaining blood glucose and body weight during nutritional deficiencies. Recent studies have demonstrated that AgRP neurones are involved in metabolic and behavioural adaptation to an energy deficit to improve survival. In the present study, we used a neuronal subtype‐specific GHS‐R knockout mouse (AgRP‐Cre;Ghsrf/f) to investigate the role of GHS‐R in hypothalamic AgRP neurones in metabolic and behavioural adaptation to hypocaloric restricted feeding. We subjected the mice to a restricted feeding regimen of 40% mild calorie restriction (CR), with one‐quarter of food allotment given in the beginning of the light cycle and three‐quarters given at the beginning of the dark cycle, to mimic normal mouse intake pattern. The CR‐fed AgRP‐Cre;Ghsrf/f mice exhibited reductions in body weight, fat mass and blood glucose. Metabolic profiling of these CR‐fed AgRP‐Cre;Ghsrf/f mice showed a trend toward reduced basal metabolic rate, significantly reduced core body temperature and a decreased expression of thermogenic genes in brown adipose tissue. This suggests a metabolic reset to a lower threshold. Significantly increased physical activity, a trend toward increased food anticipatory behaviour and altered fuel preferences were also observed in these mice. In addition, these CR‐fed AgRP‐Cre;Ghsrf/f mice exhibited a decreased counter‐regulatory response, showing impaired hepatic glucose production. Lastly, hypothalamic gene expression in AgRP‐Cre;Ghsrf/f mice revealed increased AgRP expression and a decreased expression of genes in β‐oxidation pathways. In summary, our data suggest that GHS‐R in AgRP neurones is a key component of the neurocircuitry involved in metabolic adaptation to calorie restriction.

show abstract

Section: Discussioncontrasting

confidence: 49%

Ghrelin receptor in agouti‐related peptide neurones regulates metabolic adaptation to calorie restriction

Bongmba

Lee

et al. 2019

J Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…Further assessments should be done over a more detailed and careful time course. The PVN is also a critical area that integrates the ghrelin signal with various neuropsychological factors (Dos‐Santos, Reis, Perello, Ferguson, & Mecawi, 2019). However, no in vivo studies have studied neuronal activity in the PVN when combined with peripherally administered ghrelin and stress loading.…”

Section: Discussionmentioning

confidence: 99%

Vulnerability to psychological stress‐induced anorexia in female mice depends on blockade of ghrelin signal in nucleus tractus solitarius

Yamada

Iizuka

Nahata

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

Background and Purpose Women have a higher incidence of eating disorders than men. We investigated whether the effects of ghrelin on feeding are affected by sex and stress, and to elucidate the mechanisms that may cause sex differences in stress‐mediated anorexia, focusing on ghrelin. Experimental Approach Acylated ghrelin was administered to naïve and psychologically stressed male and female C57BL/6J mice, followed by measurements of food intake and plasma hormone levels. Ovariectomy was performed to determine the effects of ovary‐derived oestrogen on stress‐induced eating disorders in female mice. The numbers of Agrp or c‐Fos mRNA‐positive cells and estrogen receptor α/c‐Fos protein‐double‐positive cells were assessed. Key Results Ghrelin administration to naïve female mice caused a higher increase in food intake, growth hormone secretion, Agrp mRNA expression in the arcuate nucleus and c‐Fos expression in the nucleus tractus solitarius (NTS) than in male mice. In contrast, psychological stress caused a more sustained reduction in food intake in females than males. The high sensitivity of naïve females to exogenous ghrelin was attenuated by stress exposure. The stress‐induced decline in food intake was not abolished by ovariectomy. Estrogen receptor‐α but not ‐β antagonism prevented the decrease in food intake under stress. Estrogen receptor‐α/c‐Fos‐double‐positive cells in the NTS were significantly increased by stress only in females. Conclusion and Implications Stress‐mediated eating disorders in females may be due to blockade of ghrelin signalling via estrogen receptor‐α activation in the NTS. Targeting the ghrelin signal in the brain could be a new treatment strategy to prevent these disorders.

show abstract

“…The orexigenic hormone ghrelin is secreted by gastric mucosa and pancreas, and its main site of action is the hypothalamic melanocortin system, consisting of the pro‐opiomelanocortin (POMC)‐expressing neurons, the neuropeptide Y (NPY), and agouti‐related peptide (AgRP)‐coexpressing neurons and neurons, expressing MC3R and MC4R (Kim, Leyva, & Diano, 2014). Ghrelin increases food intake and decreases fat oxidation, which chronically contribute to increased adiposity (Dos‐Santos, Reis, Perello, Ferguson, & Mecawi, 2019). In the hypothalamic arcuate nucleus of male SD rats, ghrelin activates the intracellular energy sensor AMPK in orexigenic NPY neurons, which leads to activation of these neurons (Kohno, Sone, Minokoshi, & Yada, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Ghrelin increases food intake and decreases fat oxidation, which chronically contribute to increased adiposity (Dos-Santos, Reis, Perello, Ferguson, & Mecawi, 2019). In the hypothalamic arcuate nucleus of male SD rats, ghrelin activates the intracellular energy sensor AMPK in orexigenic NPY neurons, which leads to activation of these neurons (Kohno, Sone, Minokoshi, & Yada, 2008).…”

Section: F I G U R Ementioning

confidence: 99%

Sex‐dependent alterations of dopamine receptor and glucose transporter density in rat hypothalamus under long‐term clozapine and haloperidol medication

et al. 2020

View full text Add to dashboard Cite

Objective Sex‐dependent disturbances of peripheral glucose metabolism are known complications of antipsychotic drug treatment. The influence of long‐term clozapine and haloperidol medication on hypothalamus, maintaining aspects of internal body homeostasis, has not yet been completely clarified. Methods After puberty, male and female Sprague Dawley rats were fed orally with ground pellets containing haloperidol (1 mg/kgBW/day) or clozapine (20 mg/kgBW/day) for 12 weeks. The hypothalamic protein expression of dopamine receptors D2R and D4R, melanocortin receptor MC4R, and glucose transporters Glut1 and Glut3 was examined. Glucose, glycogen, lactate, and pyruvate levels were determined, also malondialdehyde equivalents as markers of oxidative stress. Results D2R expression was increased in the male haloperidol and clozapine group but decreased in females medicated with clozapine. D4R expression was upregulated under clozapine medication. While females showed increased Glut1, Glut3 was elevated in both male and female clozapine‐medicated animals. We found no changes of hypothalamic malondialdehyde, glycogen, and MC4R. Hypothalamic lactate was elevated in the female clozapine group. Conclusion Clozapine sex‐dependently affects the expression of D2R, Glut1, and Glut3. The upregulation of the glucose transporters indicates glucose deprivation in the endothelial cells and consequently in astrocytes and neurons. Increased hypothalamic lactate in females under clozapine points to enhanced glycolysis with a higher glucose demand to produce the required energy. Haloperidol did not change the expression of the glucose transporters and upregulated D2R only in males.

show abstract

The actions of ghrelin in the paraventricular nucleus: energy balance and neuroendocrine implications

Cited by 18 publications

References 170 publications

Ghrelin receptor in agouti‐related peptide neurones regulates metabolic adaptation to calorie restriction

Ghrelin receptor in agouti‐related peptide neurones regulates metabolic adaptation to calorie restriction

Vulnerability to psychological stress‐induced anorexia in female mice depends on blockade of ghrelin signal in nucleus tractus solitarius

Sex‐dependent alterations of dopamine receptor and glucose transporter density in rat hypothalamus under long‐term clozapine and haloperidol medication

Contact Info

Product

Resources

About