Integration of Nutrient Sensing in Fish Hypothalamus

Soengas, José L.

doi:10.3389/fnins.2021.653928

Cited by 42 publications

(34 citation statements)

References 103 publications

(172 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previous studies were mostly focused on leptin [51,52] and NPY [53] as modulators of hypothalamic CREB, our finding extends the current knowledge, showing that a nutrient is also capable of regulating hypothalamic CREB. This is in line with data showing that CREB integrates a nutrient-sensing system in the hypothalamus of fish [54].…”

Section: Discussionsupporting

confidence: 92%

Hypothalamic CREB Regulates the Expression of Pomc-Processing Enzyme Pcsk2

Zanesco

Mendes

Engel

et al. 2022

Cells

View full text Add to dashboard Cite

Background: The hypothalamic proopiomelanocortin (Pomc) neurons act as first-order sensors of systemic energy stores, providing signals that regulate caloric intake and energy expenditure. In experimental obesity, dietary saturated fatty acids affect Pomc endopeptidases (PCs), resulting in the abnormal production of the neurotransmitters α-melanocyte-stimulating hormone (α-MSH) and β-endorphin, thus impacting energy balance. The cAMP response element-binding protein (CREB) is one of the transcription factors that control the expression of Pomc endopeptidases; however, it was previously unknown if dietary fats could affect CREB and consequently the expression of Pomc endopeptidases. Methods: Here, we used single-cell RNA sequencing analysis, PCR, immunoblot, ELISA and immunofluorescence histological assays to determine the impact of a high-fat diet (HFD) on the expression and function of hypothalamic CREB and its impact on the melanocortinergic system. Results: The results indicate that CREB is expressed in arcuate nucleus Pomc neurons and is activated as early as nine hours after the introduction of a high-fat diet. The inhibition of hypothalamic CREB using a short-hairpin RNA lentiviral vector resulted in increased diet-induced body-mass gain and reduced energy expenditure. This was accompanied by reduced expression of the Pomc endopeptidases, protein convertase 2, which are encoded by Pcsk2, and by the loss of the high-fat-diet-induced effect to inhibit the production of α-MSH. Conclusions: This study provides the first evidence for the involvement of CREB in the abnormal regulation of the hypothalamic Pomc endopeptidase system in experimental obesity.

show abstract

Section: Discussionsupporting

confidence: 92%

Hypothalamic CREB Regulates the Expression of Pomc-Processing Enzyme Pcsk2

Zanesco

Mendes

Engel

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Therefore, the binding profile of Brex to these four receptors (D2R, 5-HT1AR, 5-HT7R, and H1R) alone cannot fully explain the effects of Brex on AMPK signalling or cAMP synthesis in the hypothalamus. Additionally, both Akt and Erk signallings also contribute poorly to the effects of Brex on AMPK signalling since these signallings form a negative feedback loop with AMPK signalling [ 74 , 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

Brexpiprazole Reduces 5-HT7 Receptor Function on Astroglial Transmission Systems

Fukuyama

Motomura

Okada

2022

IJMS

View full text Add to dashboard Cite

Several atypical antipsychotics exert mood-stabilising effects via the modulation of various monoamine receptors and intracellular signallings. Recent pharmacodynamic studies suggested that tripartite synaptic transmission can contribute to the pathophysiology of schizophrenia and mood disorders, their associated cognitive impairment, and several adverse reactions to atypical antipsychotics. Therefore, to explore the mechanisms underlying the antidepressive mood-stabilising and antipsychotic effects of brexpiprazole (Brex), we determined the effects of subchronic administration of therapeutically relevant concentrations/doses of Brex on the protein expression of 5-HT receptors, connexin43, cAMP levels, and intracellular signalling in cultured astrocytes and rat hypothalamus using ultra-high-pressure liquid chromatography with mass spectrometry and capillary immunoblotting systems. Subchronic administration of a therapeutically relevant concentration of Brex (300 nM) downregulated both 5-HT1A (5-HT1AR) and 5-HT7 (5-HT7R) receptors, in addition to phosphorylated Erk (pErk), without affecting phosphorylated Akt in the astroglial plasma membrane. Subchronic administration of 300 nM Brex decreased and increased phosphorylated AMPK and connexin43, respectively, in the astroglial cytosol fraction. A therapeutically relevant concentration of Brex acutely decreased the astroglial cAMP level, whereas, under the inhibition of 5-HT1AR, Brex did not affect astroglial cAMP levels. However, the 5-HT7R-agonist-induced increased astroglial cAMP level was inhibited by Brex. In contrast to the in vitro study, systemic subchronic administration of effective doses of Brex (3 and 10 mg/kg/day for 14 days) increased the cAMP level but did not affect phosphorylated AMPK in the rat hypothalamus. These results suggest several complicated pharmacological features of Brex. Partial 5-HT1AR agonistic action predominates in the low range of therapeutically relevant concentrations of Brex, whereas in the high range, 5-HT7R inverse agonist-like action is overlapped on the 5-HT1A agonistic action. These unique suppressive effects of Brex on 5-HT7R play important roles in the clinical features of Brex regarding its antidepressive mood-stabilising actions.

show abstract

“…In fish, CREB is suggested to be involved in MOP downstream mechanisms in zebrafish ( Jimenez-Gonzalez et al, 2016 ). Considering that CREB phosphorylation status usually decrease in fish brain under conditions eliciting a decrease in food intake ( Soengas, 2021 ), we could suggest that an increased CREB phosphorylation is involved in opioid mechanisms in telencephalon of rainbow trout.…”

Section: Discussionmentioning

confidence: 99%

“…The homeostatic signals arise from the necessity of maintaining body energy, while hedonic signaling results from pleasure and/or sensory perception. Both types of signals are integrated in brain regions notably in hypothalamus and telencephalon ( Delgado et al, 2017 ; Soengas, 2021 ). The knowledge about regulation of food intake in fish is mostly restricted to homeostatic mechanisms.…”

Section: Introductionmentioning

confidence: 99%

The Opioid System in Rainbow Trout Telencephalon Is Probably Involved in the Hedonic Regulation of Food Intake

et al. 2022

Self Cite

View full text Add to dashboard Cite

We hypothesize that opioids are involved in the regulation of food intake in fish through homeostatic and hedonic mechanisms. Therefore, we evaluated in rainbow trout (Oncorhynchus mykiss) hypothalamus and telencephalon changes in precursors, endogenous ligands and receptors of the opioid system under different situations aimed to induce changes in the homeostatic (through fasted/fed/refed fish) and hedonic (through feeding fish a control or a palatable high-fat diet) regulation of food intake. No major changes occurred in parameters assessed related with the nutritional condition of fish (fasted/fed/refed), allowing us to suggest that the opioid system seems not to have an important role in the homeostatic regulation of food intake in rainbow trout. The responses observed in telencephalon of rainbow trout fed the palatable high-fat diet included a decrease in mRNA abundance of the opioid precursor penka, in a way similar to that known in mammals, and increased mRNA abundance of the opioid receptors oprd1 and oprk1 supporting a role for telencephalic opioid system in the hedonic regulation of food intake in fish.

show abstract

Integration of Nutrient Sensing in Fish Hypothalamus

Cited by 42 publications

References 103 publications

Hypothalamic CREB Regulates the Expression of Pomc-Processing Enzyme Pcsk2

Hypothalamic CREB Regulates the Expression of Pomc-Processing Enzyme Pcsk2

Brexpiprazole Reduces 5-HT7 Receptor Function on Astroglial Transmission Systems

The Opioid System in Rainbow Trout Telencephalon Is Probably Involved in the Hedonic Regulation of Food Intake

Contact Info

Product

Resources

About