ABSTRACT
Obesity arising due to the dietary and life style changes is fast reaching epidemic proportions all over the world. There is increasing evidence that the incidence of Alzheimer disease (AD) is significantly influenced by a cluster of metabolic diseases, including diabetes and obesity. This study was aimed to test the suitability of experimentally-induced obesity in rats as an experimental animal model of AD. We used the procedure of neonatal administration of rats with monosodium L-glutamate (MSG), which generates adult obese animals as our study design and assessed the AD-like changes by measuring amyloid ß (1-42) and acetylcholinesterase (AChE) levels in the hippocampal extracts and cognitive impairments by Barnes maze task. Further, we investigated the influence of anti-obesity substance [D-Lys (3)] GHRP-6 on blood glucose, hippocampal Aß, AChE levels and restoration of cognitive deficits. Results revealed that administration of MSG to neonatal rats exhibited increased body mass index and serum glucose levels over the controls. Measurement of markers for AD-like molecular changes i.e. amyloid ß (Aß) and AChE levels showed marked elevation in these two parameters in the hippocampus of MSG-treated rats. Assessment of cognitive abilities by Barnes maze revealed spatial disorientation characteristic of AD. Administration of ghrelin receptor analog [D-Lys (3)] GHRP-6 to obese rats resulted in significant restoration of serum cholesterol, glucose, leptin and ghrelin levels to that of control with concomitant reduction in hippocampal Aß and AChE levels. In addition, the treated animals exhibited marked improvement in Barne’s maze task. These findings suggest that MSG-induced obese rats may serve as non-transgenic animal model for AD research. Further, the results indicate the potential of [D-Lys (3)] GHRP-6 as a promising anti-Alzheimer candidate.
Subject(s)
Amyloid beta-Peptides/metabolism , Animals , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Male , Obesity/metabolism , Oligopeptides/physiology , Rats , Rats, Sprague-DawleyABSTRACT
Aims: The salty taste modality is modulated by epithelial sodium channel (ENaC) and Transient Receptor Potential Vanniloid (TRPV1) ionic channel and more recently, the gastric hormone ghrelin and its signaling system are also thought to play a role. Taste perception plays an important role in modulating food preference, and intake and is partly determined by genetic variations in chemoreceptor genes. For the salty taste modality, no studies have yet identified any genetic determinants of salt taste in humans. Nevertheless, a single study has identified that common variations in genes encoding for TRPV1 (TRPV1) and ENaC (SCNN1B) may influence the perception of salt solutions in humans, while it is currently unknown whether it would be the same for ghrelin and its cognate receptor, GHSR. Therefore, the primary objective of this study was to investigate the association of Ghrelin Gly90Leu and GHSR Gly57Gly gene polymorphisms with individual’s saltiness intensity perception and pleasantness ratings. Study Design: A convenience sampling method was practiced in this study. The sampling was carried out among students between the age of 18–25. Place and Duration of Study: Universiti Tunku Abdul Rahman (UTAR), Perak campus between January to December, 2011. Methodology: We recruited 166 Malaysian university students (mean age: 20.33±1.68; 75 males, 91 females; 152 ethnic Chinese, 14 Indians; 113 normal weight, 53 overweight) by convenience sampling. Low and high sodium concentrations of foods, solutions and broths were tasted and rated for their perceived intensity and pleasantness using generalized Labeled Magnitude Scale and Labeled Affective Magnitude scale, respectively. Results: The minor allele frequencies (MAF) of Ghrelin Gly90Leu and GHSR Gly57Gly were 0.48 and 0.31, respectively. Only the perceived intensity of salted egg was significantly different among Ghrelin Gly90Leu genotypes, where the individuals with T318T and A318T genotypes rated the intensity significantly higher than those with the A318A genotype. Conclusion: In conclusion, Ghrelin Gly90Leu and GHSR Gly57Gly SNPs did not serve as markers for individual’s saltiness intensity perception and pleasantness ratings, at least among Malaysian subjects in this study. This suggests that the ghrelin signaling mechanism in modulating salty taste responsivity in inconclusive at the moment, as the positive findings in mice might not be translatable to humans.
ABSTRACT
Objective : The present study investigated the effects of different dosages of a GHS-R antagonist [D-Lys3] on some serum hormonal (cortisol, T3 and T4) and biochemical parameters in a rat.Materials and methods : Thirty-six 60-day-old male rats were assigned to four treatments. [D-Lys3]-GHRP-6 solutions were infused via intraperitoneal injections. Blood was collected and analyzed.Results : The large dosages of a GHS-R antagonist (200 ng/kg BW) caused increases in cortisol, whereas no significant changes occurred when low dosages were injected. There were no significant changes in T3 and T4 following the administration of the GHS-R antagonist, but a considerable increase was observed in blood glucose levels of the groups (G50, G100, and G200 ng/kg BW). There was a significant increase in total protein when the greatest dose was administrated (G200 ng/kg BW). However, total cholesterol, triglycerides, and albumin showed no significant changes.Conclusions : Exogenous GHS-R antagonist can cause an increase in glucose and moderate increases in cortisol and total protein, yet it has no significant effect on T3 and T4 levels or on the concentrations of serum lipids. The effect of GHS-R antagonist is not completely adverse to the effects of ghrelin. Further molecular studies are necessary to identify the physiological effects of the peptidic GHS-R antagonist. Arq Bras Endocrinol Metab. 2014;58(3):288-91.
Objetivo : O presente estudo investigou os efeitos de diferentes doses do antagonista do GHS-R [D-Lys3] sobre alguns parâmetros hormonais (cortisol, T3 e T4) e bioquímicos em ratos.Materiais e métodos : Trinta e seis ratos machos com 60 dias de idade foram alocados para quatro tratamentos. Soluções de [D-Lys3]-GHRP-6 foram administradas por meio de injeções intraperitoneais e foram coletadas e analisadas amostras.Resultados : Doses altas de antagonista de GHS-R (200 ng/kg PC) levaram a aumento do cortisol, enquanto não houve diferença significativa quando foram injetadas doses baixas. Não houve alterações significativas em T3 e T4 depois da administração do antagonista do GHS-R, mas foi observado aumento considerável nos níveis de glicose sanguínea dos grupos (G50, G100 e G200 ng/kg PC). Houve aumento significativo na proteína total quando foi administrada a maior dose (G200 ng/kg PC), entretanto, não foram observadas alterações no colesterol total, nos triglicérides e na albumina.Conclusões : O antagonista do GHS-R exógeno pode causar aumento da glicose e aumento moderado do cortisol e proteína total, embora não haja efeitos significativos nos níveis de T3 e T4 ou na concentração de lipídios séricos. O efeito do antagonista de GHS-R não é completamente adverso aos efeitos da grelina. Devem ser feitos outros estudos moleculares para se identificar os efeitos fisiológicos do peptídeo antagonista do GHS-R. Arq Bras Endocrinol Metab. 2014;58(3):288-91.