Aging and Diets Regulate the Rat Anterior Pituitary and Hypothalamic Transcriptome

Bédard, Karine; Bédard, Julie; Rocheleau, Ghislain; Ferland, Guylaine; Gaudreau, Pierrette

doi:10.1159/000338411

Cited by 13 publications

(7 citation statements)

References 60 publications

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“…45 Enhanced ghrelin signaling improved the levels of neuronal genes involved in inflammation, apoptosis, DNA repair and migration in the hypothalamus of klotho-deficient mice. These findings are consistent with previous reports in which the beneficial effect of CR on age-related hypothalamic gene changes 46 and the neuroprotective effect of ghrelin 47 were observed. Cancer and dementia are the most debilitating conditions associated with aging.…”

Section: Discussionsupporting

confidence: 94%

Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1

et al. 2016

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Caloric restriction (CR) is known to retard aging and delay functional decline as well as the onset of diseases in most organisms. Ghrelin is secreted from the stomach in response to CR and regulates energy metabolism. We hypothesized that in CR ghrelin has a role in protecting aging-related diseases. We examined the physiological mechanisms underlying the ghrelin system during the aging process in three mouse strains with different genetic and biochemical backgrounds as animal models of accelerated or normal human aging. The elevated plasma ghrelin concentration was observed in both klotho-deficient and senescence-accelerated mouse prone/8 (SAMP8) mice. Ghrelin treatment failed to stimulate appetite and prolong survival in klotho-deficient mice, suggesting the existence of ghrelin resistance in the process of aging. However, ghrelin antagonist hastened death and ghrelin signaling potentiators rikkunshito and atractylodin ameliorated several age-related diseases with decreased microglial activation in the brain and prolonged survival in klotho-deficient, SAMP8 and aged ICR mice. In vitro experiments, the elevated sirtuin1 (SIRT1) activity and protein expression through the cAMP–CREB pathway was observed after ghrelin and ghrelin potentiator treatment in ghrelin receptor 1a-expressing cells and human umbilical vein endothelial cells. Furthermore, rikkunshito increased hypothalamic SIRT1 activity and SIRT1 protein expression of the heart in the all three mouse models of aging. Pericarditis, myocardial calcification and atrophy of myocardial and muscle fiber were improved by treatment with rikkunshito. Ghrelin signaling may represent one of the mechanisms activated by CR, and potentiating ghrelin signaling may be useful to extend health and lifespan.

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Section: Discussionsupporting

confidence: 94%

Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1

et al. 2016

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“…In fact, diabetes has been associated with declining cognitive performance in aging (Umegaki et al, 2013), and elevated levels of circulating glucose and insulin, as found in OAL SD rats, are prevented by LTCR (Bedard et al, 2010). In AL male SD rats, aging was associated with a large BW gain as previously reported (Bedard et al, 2010, 2013; Moyse et al, 2012). In 20-month-old AL rats, BW was 216% higher than in YAL rats, and LTCR prevented this increase [Figure 3A, One-Way ANOVA, F (2, 21) = 73.49, p < 0.0001, n = 5–11].…”

Section: Resultssupporting

confidence: 77%

“…Rats had free access to chow, except for CR rats, and water. At 7.5 months, SD rats were subjected or not to 20% caloric restriction for 2 weeks and 40% thereafter until death (Bedard et al, 2010, 2013; Moyse et al, 2012). AL and CR SD rats were fed chow Teklad control diet TD04088 and fortified TD 04089, respectively, to ensure that the two groups receive equivalent amounts of minerals and vitamins (Harlan Teklad, Madison, WI), as previously described (Moyse et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

“…In the present study, the effects of aging and body mass on recognition and spatial memory, anxious behaviors and related synaptic plasticity was investigated using two models of successful aging: the obesity-resistant LOU rat (Alliot et al, 2002) and the Sprague Dawley (SD) rat subjected to long-term caloric restriction (LTCR) (Bedard et al, 2010, 2013; Moyse et al, 2012). LTCR, the most powerful nutritional intervention known to increase longevity in good health, has been associated with enhanced hippocampal plasticity in rodents (Stranahan and Mattson, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

Ménard

Quirion

Bouchard

et al. 2014

Front. Aging Neurosci.

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The LOU/C/Jall (LOU) rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW) throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6-42 months) were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning, and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL) male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR) prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR) rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn), an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non-obese aging rats.

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“…This last element is extremely important to understand the establishment and the development of obesity by studying key molecular signals at different steps and reveal the underlying paths. Importantly, the data generated on preferentially expressed genes in the hypothalamus and pituitary gland [ 125 , 126 ] improve the understanding of the central control of energy metabolism and diet impact on gene expression.…”

Section: Diet-related Genes: a Focus On High-fat Diet To Identify mentioning

confidence: 99%

Exercise and High-Fat Diet in Obesity: Functional Genomics Perspectives of Two Energy Homeostasis Pillars

Ghanemi

Melouane

Yoshioka

et al. 2020

Genes

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The heavy impact of obesity on both the population general health and the economy makes clarifying the underlying mechanisms, identifying pharmacological targets, and developing efficient therapies for obesity of high importance. The main struggle facing obesity research is that the underlying mechanistic pathways are yet to be fully revealed. This limits both our understanding of pathogenesis and therapeutic progress toward treating the obesity epidemic. The current anti-obesity approaches are mainly a controlled diet and exercise which could have limitations. For instance, the “classical” anti-obesity approach of exercise might not be practical for patients suffering from disabilities that prevent them from routine exercise. Therefore, therapeutic alternatives are urgently required. Within this context, pharmacological agents could be relatively efficient in association to an adequate diet that remains the most efficient approach in such situation. Herein, we put a spotlight on potential therapeutic targets for obesity identified following differential genes expression-based studies aiming to find genes that are differentially expressed under diverse conditions depending on physical activity and diet (mainly high-fat), two key factors influencing obesity development and prognosis. Such functional genomics approaches contribute to elucidate the molecular mechanisms that both control obesity development and switch the genetic, biochemical, and metabolic pathways toward a specific energy balance phenotype. It is important to clarify that by “gene-related pathways”, we refer to genes, the corresponding proteins and their potential receptors, the enzymes and molecules within both the cells in the intercellular space, that are related to the activation, the regulation, or the inactivation of the gene or its corresponding protein or pathways. We believe that this emerging area of functional genomics-related exploration will not only lead to novel mechanisms but also new applications and implications along with a new generation of treatments for obesity and the related metabolic disorders especially with the modern advances in pharmacological drug targeting and functional genomics techniques.

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Aging and Diets Regulate the Rat Anterior Pituitary and Hypothalamic Transcriptome

Cited by 13 publications

References 60 publications

Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1

Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1

Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

Exercise and High-Fat Diet in Obesity: Functional Genomics Perspectives of Two Energy Homeostasis Pillars

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