Mus musculus
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ABSTRACT:
PROVIDER: PRJNA111565 | ENA |
REPOSITORIES: ENA
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Project description:In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced bodyweight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. We present evidence that these phenotypes, which are associated to increased lifespan in the Eps8 null mice, are due to caloric restriction. This, in turn, is caused by reduced intestinal fat absorption, due to altered morphogenesis of microvilli in intestinal enterocytes. In the nematode, genetic removal of Eps8, causes a microvillar phenotype, indistinguishable from that observed in mice, which leads to early larval lethality. By exploiting the nematode model system, we demonstrate here that the actin bundling activity of Eps8 is indispensable for viability and proper intestinal morphogenesis. This result links a precise molecular function of Eps8 to proper microvillar morphogenesis, and therefore to the phenotype of Eps8-null mice. Our results implicate actin dynamics in individual variations in bodyweight, metabolic status and longevity. cDNA expression profiling of liver of 4 mutant EPS8 -/- animals versus pool of 4 wt animals. 8 hybridisation including 4 dye swap experiments
2010-03-09 | E-GEOD-14454 | biostudies-arrayexpress
Project description:In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced bodyweight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. We present evidence that these phenotypes, which are associated to increased lifespan in the Eps8 null mice, are due to caloric restriction. This, in turn, is caused by reduced intestinal fat absorption, due to altered morphogenesis of microvilli in intestinal enterocytes. In the nematode, genetic removal of Eps8, causes a microvillar phenotype, indistinguishable from that observed in mice, which leads to early larval lethality. By exploiting the nematode model system, we demonstrate here that the actin bundling activity of Eps8 is indispensable for viability and proper intestinal morphogenesis. This result links a precise molecular function of Eps8 to proper microvillar morphogenesis, and therefore to the phenotype of Eps8-null mice. Our results implicate actin dynamics in individual variations in bodyweight, metabolic status and longevity.
2010-03-09 | GSE14454 | GEO
Project description:Background & Aims: In this study, we investigated metabolic and molecular effects of weekly intervening 30% calorie restriction on long term natural progression of non-alcoholic fatty liver disease (NAFLD), which was induced by a medium fat diet. Methods: Male C57BL/6J mice of 9 weeks old received either (1) a control (C), (2) a calorie restricted (CR), (3) a medium fat (MF; 25%fat) or (4) an intermittent diet (ID), a weekly alternating diet consisting of calorie restriction and medium fat diet ad libitum until sacrifice at the age of 12 months. Various metabolic and molecular features of the liver were examined. Results: The ID regimen improved the status of a range of metabolic parameters and showed no progression to NAFLD: proper glucose tolerance, low hepatic triglyceride content, low plasma alanine aminotransferase and no abnormalities in its liver morphological features; similarly to that of CR. In contrast, the metabolic parameters in a number of the C and MF animals indicated development of NAFLD and hepatic fibrosis, which was positively correlated with body weight. Despite the metabolic phenotypes similarity, the liver gene expression profile of ID-fed mice did not reflect that of CR mice and resembled more to C and MF-fed mice with similar low body weight. Conclusions: Our study reveals that ID is beneficial for metabolic health and prevents the development of NAFLD in mice, with a gene expression profile similar to C and MF diet in a body weight-dependent manner.
2018-05-09 | GSE53188 | GEO
Project description:Leanness is associated with increased lifespan and is linked to favorable metabolic conditions promoting life extension. We show here that deficiency of the lipid synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), which reduces body fat in mice, promotes longevity. Female DGAT1-deficient mice were protected from age-related increases in body fat, non-adipose tissue triglycerides, and markers of inflammation in white adipose tissue. These metabolic changes were accompanied by an increased mean and maximal lifespan of ~25% and ~10%, respectively. The gene expression profile of DGAT1-deficient mice was not highly correlated with calorie restriction of sex and age matched wild-type littermates. Our findings indicate that loss of DGAT1-mediated lipid synthesis results in leanness, protects against age-related metabolic consequences, and thus extends longevity. Liver gene expression profiles between short-term calorie restricted wild-type (WTCR) and Dgat1 deficient (KO) middle-aged (15-16 mo) female mice were compared to determine if calorie restriction and Dgat1 deficiency rely on common regulatory pathways for the promotion of longevity. Both CR and KO were compared to middle-aged wild-type female littermates fed a standard chow diet ad libitum (WTAL).
2012-02-09 | E-GEOD-26267 | biostudies-arrayexpress
Project description:Resveratrol is a naturally occurring compound that profoundly affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here we treated 10 healthy, obese men with placebo and 150 mg/day resveratrol in a randomized double-blind cross-over study for 30 days. Resveratrol supplementation significantly reduced sleeping- and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1alpha protein levels, increased citrate synthase activity, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels, and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces profound metabolic changes in obese subjects, mimicking the effects of calorie restriction. double-blind randomized cross-over study, Expression profiling by microarray
2011-11-08 | E-GEOD-32357 | biostudies-arrayexpress
Project description:In utero undernutrition is associated with obesity and insulin resistance, although its effect on skeletal muscle remains poorly defined. We report that, in mice, adult offspring from undernourished dams have decreased energy expenditure, decreased skeletal muscle mitochondrial content, and altered energetics in isolated mitochondria and permeabilized muscle fibers. Strikingly, when these mice are put on a 40% calorie restricted diet they lose half as much weight as calorie restricted controls. Our results reveal for the first time that in utero undernutrition alters metabolic physiology having a profound effect on skeletal muscle energetics and response to calorie restriction in adulthood. We have used a mouse model of low birth weight generated through 50% food restriction of mouse dams during the third week of gestation. We have studied in utero food restricted offspring and control offspring that were not food restricted in utero in both the ad libitum and calorie restricted states. Gene expression profiling was performed on tibialis anterior muscle from 8 mice per group, pooled in pairs.
2014-08-01 | E-GEOD-53520 | biostudies-arrayexpress
Project description:Resveratrol is a naturally occurring compound that profoundly affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here we treated 10 healthy, obese men with placebo and 150 mg/day resveratrol in a randomized double-blind cross-over study for 30 days. Resveratrol supplementation significantly reduced sleeping- and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1alpha protein levels, increased citrate synthase activity, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels, and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces profound metabolic changes in obese subjects, mimicking the effects of calorie restriction.
2011-11-08 | GSE32357 | GEO
Project description:lean control, obese, and formerly obese C57BL6N mice which underwent weight loss via vertical sleeve gastrectomy or calorie restriction were injected with E0771 cells and tumor growth was monitored
2023-09-12 | GSE230471 | GEO
Project description:Aims/hypothesis: Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of the metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to identify whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. Methods: We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. A total of 21 individuals diagnosed with the metabolic syndrome was randomly assigned for caloric restriction (CR; n = 11, mean age 49 ± 8.5 years, female 63%; diet of 5,941 ± 686 KJ per day) or isocaloric dietary protein restriction (PR; n = 10, mean age 51.6 ± 8.9 years, female 50%; diet of 8,409 ± 2,360 KJ per day) and followed for 27 days. Results: Like CR, PR promoted weight loss (-6.6%, P= 0.0041) due to reduction in adiposity (-9.9%, P= 0.0007), associated with reductions in blood glucose (-52.7%, P= 0.0002), lipid levels (cholesterol, -35.4%, P= 0.0010; triglycerides, -39.5% P= 0.0022) and blood pressure (systolic, -37.7 P< 0.0001; diastolic, -73.2% P< 0.0001). PR resulted in enrichment of metabolic pathways related to the immune system such as B cell proliferation, lymphocyte proliferation and leukocyte proliferation in subcutaneous adipose tissue. Hence, a reduction in calorie intake or changes in the gut microbiome are not necessary to confer the metabolic benefits of DR. Instead, a reduction in protein intake with a mild increase in carbohydrate intake to maintain the isocaloric balance of the diet is sufficient to improve metabolic control. Conclusions/interpretation: Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has greater potential to be used as adjuvant therapy for people with the metabolic syndrome.
2022-06-20 | GSE192587 | GEO
Project description:Cultivation methods used to investigate microbial calorie restriction often result in carbon and energy starvation. This study aims to dissect cellular responses to calorie restriction and starvation in Saccharomyces cerevisiae by using retentostat cultivation. In retentostats, cells are continuously supplied with a small, constant carbon and energy supply, sufficient for maintenance of cellular viability and integrity but insufficient for growth. When glucose-limited retentostats cultivated under extreme calorie restriction were subjected to glucose starvation, calorie-restricted and glucose-starved cells were found to share characteristics such as increased heat-shock tolerance and expression of quiescence-related genes. However, they also displayed strikingly different features. While calorie-restricted yeast cultures remained metabolically active and viable for prolonged periods of time, glucose starvation resulted in rapid consumption of reserve carbohydrates, population heterogeneity due to appearance of senescent cells and, ultimately, loss of viability. Moreover, during starvation, calculated rates of ATP synthesis from storage carbohydrates were 2-3 orders of magnitude lower than steady-state ATP-turnover rates calculated under extreme calorie restriction in retentostats. Stringent reduction of ATP turnover during glucose starvation was accompanied by a strong down-regulation of genes involved in protein synthesis. These results demonstrate that extreme calorie restriction and carbon starvation represent different physiological states in S. cerevisiae. The yeast was first grown for 14 days under extreme calorie restriction in anaerobic, glucose-limited retentostats (Boender et al., 2009, Appl.Environ.Microbiol., 75: 5607-5614.). Subsequently, starvation was started by terminating the glucose feed. Yeast transcriptional reprogramming in response to calorie restriction and starvation was monitored by microarray analysis. Independent duplicate retentostat cultures, and subsequently starvation, were sampled for transcriptome analysis using Affymetrix microarrays. One time-point was sampled during calorie restriction (T0) and four time points were sampled during the starvation phase 10, 30, 60 and 120 minutes after switching of the feed, resulting in a dataset of 10 arrays.
2011-08-15 | E-GEOD-22602 | biostudies-arrayexpress