Project description:This study aims to elucidate nutrient dependent changes to the circadian transcriptome of whole flies. In particular, we aim to identify how dietary restriction influence circadian transcriptional output. Circadian analyses were performed to invesitigate diet-dependent changes in the number of circadian transcripts as well as their phases and circadian amplitude.
Project description:Circadian and metabolic processes are codependent. This experiment was designed to understand how a high fat diet affects circadian gene expression in the liver. Circadian gene expression in the liver is necessary for energy balance. Animals consuming normal chow or high fat diet (60% kcal from fat) for ten weeks were analyzed for circadian gene expression. Livers were harvested from animals every four hours throughout the circadian cycle.
Project description:Circadian and metabolic processes are codependent. This experiment was designed to understand how a high fat diet affects circadian gene expression in the liver. Circadian gene expression in the liver is necessary for energy balance.
Project description:The circadian gene expression in peripheral tissue displays rhythmicity which is reprogrammed by feeding rhythms and dietary composition in mammals. In this study, circadian transcriptome was performed to investigate how high fat diet influences circadian gene regulation in the mouse kidney.
Project description:Our objective was to identify candidate genes that contribute to the long 31-hour circadian period previously observed in DGRP_892. We performed transcriptional profiling of whole fly heads from two genotypes: DGRP_892, and Canton-S B, a line with a normal 24-hour circadian period. We collected fly heads every two hours over a 24-hour period. We quantified differential expression among genotype, time, and sex.
Project description:High fat diet (HFD), if prolonged, leads to obesity thereby accelerating the development of many ageing-related pathologies including chronic inflammation, cardiovascular disease, diabetes, and a higher predisposition to develop cancer. We asked whether HFD could reprogram the circadian output of young stem cells in a manner similar to what we observed during physiological ageing. HFD has been recently shown to induce a rewiring of the liver circadian transcriptome and metabolome, although in an obesity-independent manner. We therefore fed young (8 week old) C57Bl6 mice with HFD or its control diet for 7-weeks, a time when mice had not yet become obese, and performed circadian transcriptome analysis.
Project description:Even after decades of living in the same laboratory environment two Drosophila melanogaster strains originating from North America (Canton-S) and Central Russia (D18) demonstrate a few differentially expressed genes some of which may be important for local adaptation (e.g. genes responsible for insecticide resistance). Genes with different level of expression between Canton-S and D18 strains belong to important metabolic pathways, for instance energy metabolism, carbohydrate metabolic process, locomotion, body temperature rhythm regulation and tracheal network architecture. We used microarrays to make transcriptome profiling of two laboratory strains of different geographical origin after long-term laboratory maintenance
Project description:The 4 allele of Apolipoprotein E (APOE4) is the strongest genetic risk factor for Alzheimer’s disease (AD), affecting approximately 68 million Americans. APOE4 carriers exhibit cerebral metabolic deficits decades before clinical onset. We previously demonstrated that ketogenic diet (KD), a low-carbohydrate, high-fat diet promoting ketone metabolism, confers cognitive benefits in aged and PS1/APP mice. Here, we evaluated the effects of KD in a humanized APOE4 AD mouse model. KD significantly improved composite cognitive performance and spatial working memory, with pronounced effects in females. Synaptic plasticity, measured via long-term potentiation (LTP), was likewise enhanced exclusively in females. Transcriptomic and protein analyses revealed KD-induced activation of CREB pathway, marked by increased phosphorylation of ERK and CREB in female brains. Moreover, KD selectively reduced pro-inflammatory cytokine levels in females. These findings demonstrate sex-specific neuroprotective effects of KD in APOE4 mice and suggest its potential therapeutic role in mitigating AD risk in APOE4-positive women.
Project description:Maternal obesity has long-term effects on offspring metabolic health. Among the potential mechanisms, prior research has indicated potential disruptions in circadian rhythms and gut microbiota in the offspring. To challenge this hypothesis, we implemented a maternal high fat diet regimen before and during pregnancy, followed by a standard diet after birth. Our findings confirm that maternal obesity impacts offspring birth weight and glucose and lipid metabolisms. However, we found minimal impact on circadian rhythms and microbiota that are predominantly driven by the feeding/fasting cycle. Notably, maternal obesity altered rhythmic liver gene expression, affecting mitochondrial function and inflammatory response without disrupting the hepatic circadian clock. These changes could be explained by a masculinisation of liver gene expression similar to the changes observed in polycystic ovarian syndrome. Intriguingly, such alterations seem to provide the first-generation offspring with a degree of protection against obesity when exposed to a high fat diet.
Project description:Overnutrition disrupts circadian rhythms leading to dysregulated metabolism by mechanisms that are not well understood. Here we show that diet-induced obesity (DIO) causes massive remodeling of circadian enhancer activity and gene transcription in mouse liver. Remarkably, DIO triggers synchronous, high amplitude circadian rhythms of both fatty acid (FA) synthesis and oxidation. This gain of circadian rhythmicity in lipid metabolic pathways that oppose each other emphasizes the importance of balance and flux in normal hepatic lipid metabolism. DIO-promoted rhythmicity of Sterol Regulatory Element-Binding Protein (SREBP) activation, which was required not only for the induction of FA synthesis but also, surprisingly, for FA oxidation (FAO). DIO also brought about a high amplitude circadian rhythm of peroxisome proliferated receptor a (PPARa), which was required for FAO. Provision of a pharmacological ligand for PPARa abrogated the requirement of SREBP for FA oxidation (but not FA synthesis), suggesting that SREBP indirectly controls FA oxidation via production of an endogenous PPARa ligand. Moreover, the high amplitude circadian rhythm of PPARa imparts time-of-day-dependent responsiveness to lipid-lowering drugs. Thus, acquisition of rhythmicity for the non-core clock components PPARa and SREBP1 remodels metabolic gene transcription in response to a challenging nutritive environment and enables a chronopharmacological approach to metabolic disorders.