Project description:This study investigates the synergistic effects of fructose and common food preservatives (sodium benzoate, sodium nitrite, and potassium sorbate) on the development of non-alcoholic fatty liver disease (NAFLD) using a human-microbiota-associated mouse model. We examined changes in hepatic gene expression through microarray analysis to understand the molecular mechanisms underlying NAFLD progression in response to these dietary factors.
2024-08-22 | GSE275135 | GEO
Project description:microbial diversity in mouse gut affected by dietary potassium sorbate
Project description:The weak organic acid sorbic acid is a commonly used food preservative, as it inhibits the growth of bacteria, yeasts and molds. We have used genome-wide transcriptional profiling of Bacillus subtilis cells during mild sorbic acid stress to reveal the growth inhibitory activity of this preservative and to identify potential resistance mechanisms. Our analysis demonstrated that sorbic acid stressed cells induce responses normally seen upon nutrient limitation. This is indicated by the strong de-repression of the CcpA, CodY and Fur regulon, the induction of TCA cycle genes, SigL and SigH mediated genes, and the stringent response. Intriguingly, these conditions did not lead to the activation of sporulation, competence, or the general stress response (GSR). The fatty acid biosynthesis (fab) genes and BkdR regulated genes are upregulated, which may indicate plasma membrane remodeling. This was further supported by the reduced sensitivity towards the fab inhibitor cerulenin upon sorbic acid stress. We are the first to present a comprehensive analysis of the transcriptional response of B. subtilis to sorbic acid stress. Keywords: time-series, potassium sorbate response
Project description:ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age-related diseases. Here, we show that hepatic phospho-active ACLY correlates with overweight and Model for End-stage Liver Disease score in humans. Wild-type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB-204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy-fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. In vivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy-fed mice, and improved locomotion in mice exposed to cardiotoxin-induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration.
Project description:Three groups of wild-type mice were fed either a normal diet, a potassium-deficient diet, or a potassium-deficient diet while being co-treated with the AKT inhibitor MK2206 (50 mg/kg). After treatment (4 days), animals were euthanized, and kidneys were snap-frozen in liquid nitrogen.
Project description:We discovered that cellular uptake of sorbate, an FDA-approved and widely used food preservative, can induce lysine sorbylation (Ksor), a new posttranslational modification and epigenetic mark. Proteomics analysis identified over 20 histone sorbylation sites in cells and mouse liver as well as over 900 proteins in Raw264.7 cells as lysine sorbylation targets.
Project description:Libraries obtained from microdissected kidney outer medullary collecting duct from C57Bl6/J mice control or after 3 days potassium-depleted diet. Keywords: other
Project description:Recent evidence suggest that the circadian timing system plays an important role in the control of renal function and maintaining blood pressure. Here, we analyzed circadian rhythms of urinary excretion of sodium and potassium in wild-type mice and mice lacking circadian transcriptional activator clock. Analysis of urines collected at hourly intervals over a 24-hour period revealed dramatic changes in rhythms of sodium and potassium excretion in clock(-/-) mice. In parallel, significant differences in circadian pattern of plasma aldosterone levels, but not in the 24-hour mean aldosterone levels, were observed. Microarray-based profiling of renal transcriptomes demonstrated that clock(-/-) mice exhibit dysregulation in multiple mechanisms involved in maintaining sodium and potassium balance by the kidney. The most significant changes were detected in the expression levels of several key enzymes (Cyp4a14, Cyp4a12a and Cyp4a12b) required for the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a powerful regulator of renal sodium and potassium excretion, renal vascular tone and blood pressure. The 20-HETE levels measured in kidney microsomes of wild-type mice followed a circadian-like temporal pattern. In clock(-/-) mice, the acrophase of this rhythm was shifted by 8 hours and the 24-hour mean levels of 20-HETE were significantly decreased. These results demonstrate that circadian rhythms of urine electrolyte excretion are largely dependent on the circadian clock activity and indicate that circadian oscillations in renal 20-HETE content could be an important mechanism of blood pressure regulation.