Glycation-lowering compounds inhibit ghrelin signaling to reduce food intake, lower insulin resistance, and extend lifespan.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA981518 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Non-enzymatic reactions in glycolysis lead to the accumulation of methylglyoxal (MGO), a reactive precursor to advanced glycation end-products (AGEs), which has been hypothesized to drive obesity and aging-associated pathologies. A combination of nicotinamide, lipoic acid, thiamine, pyridoxamine, and piperine (Gly-Low), was identified to lower glycation by reducing MGO and MGO-derived AGE, MG-H1, in mice. Administration of Gly-Low reduced food consumption, lowered body weight, improved insulin sensitivity, and increased survival in both leptin receptor-deficient (Leprdb) and wild-type C57B6/J mice. Unlike caloric restriction, Gly-Low modulated hypothalamic signaling by upregulating mTOR pathway signaling to inhibit ghrelin-mediated hunger response. Gly-Low also slowed hypothalamic aging and increased survival when administered as a late-life intervention, suggesting its potential benefits in ameliorating age-associated decline by inducing voluntary caloric restriction and reducing glycation.
2025-02-28 | GSE234483 | GEO
Project description:We utilized single cell sequencing of FACS sorted cells from pancreatic islets of wildtype and ghrelin knock out mice to understand the effects of ghrelin deletion on gene expression profiles of various islet cells.
2023-11-06 | GSE244390 | GEO
Project description:Hepatic fibrosis, the wound-healing response to repeated liver injury, ultimately leads to cirrhosis. There is an urgent need to develop effective antifibrotic therapies. Ghrelin (encoded by Ghrl) is an orexigenic hormone that has pleiotrophic functions including protection against cell death1. Here we investigate whether ghrelin modulates liver fibrosis and protects from acute liver injury. Recombinant ghrelin reduced the fibrogenic response to prolonged bile duct ligation in rats. This effect was associated with decreased liver injury and myofibroblast accumulation as well as attenuation of the altered gene expression profile. Ghrelin also reduced fibrogenic properties in cultured hepatic stellate cells. Moreover, Ghrl-/- mice developed exacerbated hepatic fibrosis and liver damage after chronic injury. Ghrelin also protected rat livers from acute liver injury and reduced the extent of oxidative stress and the inflammatory response. In patients with chronic liver diseases, ghrelin serum levels decreased in those with advanced fibrosis and hepatic expression of the ghrelin gene correlated with expression of fibrogenic genes. Finally, in patients with chronic hepatitis C, single nucleotide polymorphisms of the ghrelin gene (-994CT and â604GA) influenced the progression of liver fibrosis. We conclude that ghrelin exerts antifibrotic effects on the liver and may represent a novel antifibrotic therapy. Experiment Overall Design: Rats were divided into three groups: control rats receiving saline (sham operation), rats with bile duct ligation receiving saline and rats with bile duct ligation receiving recombinant ghrelin (10 micrograms/Kg/day by a subcutaneous osmotic mimi-pump). For the microarray analysis samples from 6 rats were analyzed except for the ghrelin-treated group (5 rats).
2009-01-13 | E-GEOD-13747 | biostudies-arrayexpress
Project description:Ghrelin, an orexigenic gut-derived peptide, is gaining increasing attention due to its multifaceted role in a number of physiological functions, including metabolism, cardiovascular health, stress and reproduction. Ghrelin exists in circulation primarily as des-acylated and acylated ghrelin. Des-acyl ghrelin, until recently considered to be an inactive form ghrelin, is now known to have independent physiological functionality. However, the relative contribution of acyl and des-acyl ghrelin to reproductive development and function is currently unknown. Here we used ghrelin-O-acyltransferase (GOAT) knockout (KO) mice that have no measurable levels of endogenous acyl ghrelin and chronically high levels of des-acyl ghrelin, to characterise how the developmental and life-long absence of acyl ghrelin affects ovarian development and reproductive capacity. We have combined ovarian transcriptome analysis using RNA sequencing with measures of ovarian morphometry, as well as with the assessment of markers of reproductive maturity and the capacity to breed. Our data show pronounced specific changes in the ovarian transcriptome in the juvenile GOAT KO ovary, indicative of advanced ovarian development. These changes corresponded with diminished ovarian reserve in the juvenile and adult ovaries of these mice, due to a continuous reduction in the number of small follicle populations. These changes did not affect the timing of puberty onset or reproductive capacity under optimal conditions. These data suggest that an absence of acyl ghrelin does not prevent reproductive success but that appropriate levels of acyl and des-acyl ghrelin may be necessary for optimal ovarian maturation.
2019-02-05 | GSE106339 | GEO
Project description:Hepatic fibrosis, the wound-healing response to repeated liver injury, ultimately leads to cirrhosis. There is an urgent need to develop effective antifibrotic therapies. Ghrelin (encoded by Ghrl) is an orexigenic hormone that has pleiotrophic functions including protection against cell death1. Here we investigate whether ghrelin modulates liver fibrosis and protects from acute liver injury. Recombinant ghrelin reduced the fibrogenic response to prolonged bile duct ligation in rats. This effect was associated with decreased liver injury and myofibroblast accumulation as well as attenuation of the altered gene expression profile. Ghrelin also reduced fibrogenic properties in cultured hepatic stellate cells. Moreover, Ghrl-/- mice developed exacerbated hepatic fibrosis and liver damage after chronic injury. Ghrelin also protected rat livers from acute liver injury and reduced the extent of oxidative stress and the inflammatory response. In patients with chronic liver diseases, ghrelin serum levels decreased in those with advanced fibrosis and hepatic expression of the ghrelin gene correlated with expression of fibrogenic genes. Finally, in patients with chronic hepatitis C, single nucleotide polymorphisms of the ghrelin gene (-994CT and –604GA) influenced the progression of liver fibrosis. We conclude that ghrelin exerts antifibrotic effects on the liver and may represent a novel antifibrotic therapy.
2008-12-03 | GSE13747 | GEO
Project description:Glycation is a covalent protein modification that accumulates in the cellular environment. Histone proteins are particularly susceptible to glycation due to their extremely long half-lives and nucleophilic disordered tails. Here, we performed ATAC-seq on 293T cells cultured in the presence or absence of 0.5mM methylglioxal, a reactive glycolytic intermediate, for 12 hours. We demonstrate that methylglioxal treatment is associated with changes in histone occupancy and chromatin architecture globally.
2019-02-14 | GSE121252 | GEO
Project description:Ghrelin deletion and conditional ghrelin-cell ablation increase pancreatic islet size in mice
| PRJNA1022509 | ENA
Project description:Whole transcriptome analysis of Ghrelin-expressing and -descendant cells in pancreas from Nkx2.2 KO and WT mouse embryos.
2015-02-25 | E-MTAB-3353 | biostudies-arrayexpress
Project description:Ghsr-/- mice and WT controls (14 weeks-old, n = 3 / group) were used to analyse whole genome gene expression in the hippocampal DG. Briefly, mice were prepared with jugular vein cannulae attached to osmotic mini-pumps (Alzet model 2001) under isofluorane anesthesia. The mini-pumps delivered either vehicle or acyl-ghrelin (48μg/day; Phoenix Pharmaceuticals, USA) for 7 days. Mice were killed by cervical dislocation and whole brain was removed and immediately snap frozen on dry ice and stored at -80oC prior to T-RNA extraction for microarray analysis.
2022-11-01 | E-MTAB-3601 | biostudies-arrayexpress
Project description:To preliminary distinguish differential gene expressions in BPH-rat prostate after oral treatment of ghrelin.
2019-04-11 | GSE129561 | GEO