SRP145069 PRJNA392687 GSE100701 Lifelong calorie restriction and markers of colonic health in aging mice Diminishment of colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an efficient strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here we report the effects of lifelong CR on markers of colonic health in aging mice. We show that 30% energy reduction, as compared to a control (C) and moderate-fat (MF) diet, is associated with attenuated immune-related gene expression and lower levels of bile acids in the colon. Pronounced shifts in microbiota composition, together with lowered plasma levels of interleukin 6, in mice exposed to CR are in line with these findings. Furthermore, expression of genes involved in lipid metabolism was higher upon CR as compared to C and MF, pointing towards efficient regulation of energy metabolism. Switching from CR to an ad libitum MF diet at old age revealed remarkable phenotypic plasticity, although expression of a small subset of genes remained CR-associated. This research demonstrates that CR beneficially affects markers of colonic health in aging mice and as such may attenuate the progressive age-related decline in health. Overall design: Male C57BL/6J mice were randomized to different dietary regimens starting at the age of 9 weeks. Mice were lifelong fed either a semi-synthetic control diet consisting of 10E% of fat (C), a CR diet without malnutrition (30% energy reduction compared to the C diet) or a moderate-fat (MF) diet consisting of 25E% of fat. All diets, except the CR diet, were fed ad libitum. A subgroup of mice on CR was switched to the MF diet at the age of 24 months until sacrifice at 28 months. Upon sacrifice at 6 or 28 months of age, colonic scrapings were collected and RNA was isolated for microarray analyses. GSE100701 pubmed 29571009 SRP118464 PRJNA231071 GSE53188 An intermittent caloric restriction / medium fat diet protects liver from the progression of non-alcoholic fatty liver disease in C57BL/6J mice 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. Overall design: Male C57BL/6J mice were divided to 4 dietary intervention groups: Control (AIN-93W), 30% calorie restriction (CR; AIN-93W-CR), medium fat (MF; AIN-93W-MF; 25% energy from fat) and intermittent diet (ID; weekly alternating diet between AIN-93W-MF ad lib and 40% CR of AIN-93W). We treated the mice with either solvent (mock treatment) or PPARa agonist, Wy-14,643 (Wy treatment), 6 hours prior to sacrifice. The mock- and Wy-treatment were applied to body weight-matched mice within each diet group. We performed various measurements on metabolic parameters and gene expression analysis. We made a selection of animals for the microarray analysis: from each diet group we took 4 animals with lowest and highest body weight, both the mock- and Wy-treated animals. GSE53188 pubmed 25504628