Increase in hypothalamic AMPK phosphorylation induced by prolonged exposure to LPS involves ghrelin and CB1R signaling

Rivas, Priscila Marlys Sá; Vechiato, Fernanda Maria Veanholi; Borges, Beatriz de Carvalho; Rorato, Rodrigo; Antunes‐Rodrigues, José

doi:10.1016/j.yhbeh.2017.05.018

Cited by 6 publications

(2 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with previously published data, the results of RPPA analysis (Fig. 4) showed that activation of GHSR‐1a strongly affects the pattern of cellular protein phosphorylation (69, 70). This suggests that ghrelin‐induced signaling cascades may affect transcription and translation factors such as NF‐κB, ERK, mTOR, and eEF2.…”

Section: Discussionsupporting

confidence: 92%

Short‐chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling

et al. 2019

View full text Add to dashboard Cite

The gastrointestinal microbiota is emerging as a unique and inexhaustible source for metabolites with potential to modulate G-protein coupled receptors (GPCRs). The ghrelin receptor [growth hormone secretagogue receptor (GHSR)-1a] is a GPCR expressed throughout both the gut and the brain and plays a crucial role in maintaining energy balance, metabolism, and the central modulation of food intake, motivation, reward, and mood. To date, few studies have investigated the potential of the gastrointestinal microbiota and its metabolites to modulate GPCR signaling. Here we investigate the ability of short-chain fatty acids (SCFAs), lactate, and different bacterial strains, including Bifidobacterium and Lactobacillus genera, to modulate GHSR-1a signaling. We identify, for what is to our knowledge the first time, a potent effect of microbiota-derived metabolites on GHSR-1a signaling with potential significant consequences for host metabolism and physiology. We show that SCFAs, lactate, and bacterial supernatants are able to attenuate ghrelin-mediated signaling through the GHSR-1a. We suggest a novel route of communication between the gut microbiota and the host via modulation of GHSR-1a receptor signaling. Together, this highlights the emerging therapeutic potential in the exploration of the microbiota metabolome in the specific targeting of key GPCRs, with pleiotropic actions that span both the CNS and periphery.

show abstract

Section: Discussionsupporting

confidence: 92%

Short‐chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Similarly, in our study, we did not observe any significant difference in the expression of neuropeptides after LPS administration. However, as expected, administration of ghrelin agonist 10 to LPS-treated mice significantly increased the expression of orexigenic neuropeptides AgRP and NPY, as did ghrelin in rats with LPS-induced hypophagia (Rivas et al, 2017), consistent with the increased food intake.…”

Section: Discussionsupporting

confidence: 78%

In Vitro and In Vivo Characterization of Novel Stable Peptidic Ghrelin Analogs: Beneficial Effects in the Settings of Lipopolysaccharide-Induced Anorexia in Mice

Holubová

Blechová

Kákonová

et al. 2018

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Ghrelin, the only known orexigenic gut hormone produced primarily in the stomach, has lately gained attention as a potential treatment of anorexia and cachexia. However, its biologic stability is highly limited; therefore, a number of both peptide and nonpeptide ghrelin analogs have been synthesized. In this study, we provide in vitro and in vivo characterization of a series of novel peptide growth hormone secretagogue receptor (GHS-R1a) agonists, both under nonpathologic conditions and in the context of lipopolysaccharide (LPS)-induced anorexia. These analogs were based on our previous series modified by replacing the Ser with diaminopropionic acid (Dpr), the N-terminal Gly with sarcosine, and Phe with various noncoded amino acids. New analogs were further modified by replacing the n-octanoyl bound to Dpr with longer or unsaturated fatty acid residues, by incorporation of the second fatty acid residue into the molecule, or by shortening the peptide chain. These modifications preserved the ability of ghrelin analogs to bind to the membranes of cells transfected with GHS-R1a, as well as the GHS-R1a signaling activation. The selected analogs exhibited long-lasting and potent orexigenic effects after a single s.c. administration in mice. The stability of new ghrelin analogs in mice after s.c. administration was significantly higher when compared with ghrelin and [Dpr]ghrelin, with half-lives of approximately 2 hours. A single s.c. injection of the selected ghrelin analogs in mice with LPS-induced anorexia significantly increased food intake via the activation of orexigenic pathways and normalized blood levels of proinflammatory cytokines, demonstrating the anti-inflammatory potential of the analogs.

show abstract

Ghrelin attenuates oxidative stress and neuronal apoptosis via GHSR-1α/AMPK/Sirt1/PGC-1α/UCP2 pathway in a rat model of neonatal HIE

Huang

Liu

Doycheva

et al. 2019

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Increase in hypothalamic AMPK phosphorylation induced by prolonged exposure to LPS involves ghrelin and CB1R signaling

Cited by 6 publications

References 38 publications

Short‐chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling

Short‐chain fatty acids and microbiota metabolites attenuate ghrelin receptor signaling

In Vitro and In Vivo Characterization of Novel Stable Peptidic Ghrelin Analogs: Beneficial Effects in the Settings of Lipopolysaccharide-Induced Anorexia in Mice

Ghrelin attenuates oxidative stress and neuronal apoptosis via GHSR-1α/AMPK/Sirt1/PGC-1α/UCP2 pathway in a rat model of neonatal HIE

Contact Info

Product

Resources

About