The gut microbiome and blood lipid levels
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ABSTRACT:
PROVIDER: PRJEB43699 | ENA |
REPOSITORIES: ENA
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Project description:Here we show that the Drosophila nuclear receptor E78A regulates transcription in adult animals facilitating dietary lipid uptake. E78A mutant adults are viable with normal developmental timing, locomotor activity, female fecundity, but have significantly reduced stored triglycerides. This reduction in whole body triglyceride stores appears to originate from the midgut, using neutral lipid stainings we determined lipid levels in the midgut were greatly reduced. Upon examining our RNA-seq analysis we found that a gastric lipase, CG17192, is transcriptionally coordinated by E78A. CG17192 is expressed in an adult, intestinal specific fashion within control flies, and has a human ortholog. Through dietary supplementation and genetic testing we determined that the whole body hypolipidemia seen within E78A mutants is dependent on CG17192 expression within the intestine. Restoration of this lipase in the intestine of mutant flies is sufficient to restore normal lipid levels. Our data support the model that E78A contributes to a transcriptional regulation of the gastric lipase, CG17192, thus directing dietary triglyceride uptake in the adult fly.
2021-01-01 | GSE152031 | GEO
Project description:We investigated how lipid A is remodeled across the Akkermansia genus, focusing on whether structurally distinct species share common modifications and how these changes relate to antimicrobial peptide resistance. Lipid A was extracted from representative isolates spanning five Akkermansia species (A. muciniphila, A. massiliensis, A. biwaensis, A. ignis, and A. durhamii; total N=55) and profiled by negative-ion MALDI mass spectrometry using an on-target FLAT workflow. Across all species, we detected lipid A species bearing a +123 Da mass shift consistent with phosphoethanolamine (pEtN) addition, and confirmed the modification by tandem MS on dominant modified and unmodified lipid A ions. We quantified isolate-to-isolate variation in the relative abundance of pEtN-modified versus unmodified lipid A and tested functional relevance by measuring colistin susceptibility in representative strains. Higher pEtN modification ratios correlated with decreased colistin susceptibility. We further assessed regulation of this remodeling by sampling across growth phases and found that pEtN-modified lipid A increased as cultures entered stationary phase, independent of colistin exposure. Finally, we used label-free proteomics to identify cell-envelope and envelope biogenesis-associated proteins that change with growth stage in strains that do versus do not upregulate pEtN-modified lipid A, providing candidate pathways linked to outer membrane remodeling. Overall, this work reports a conserved pEtN lipid A modification across diverse Akkermansia species and connects its relative abundance to antimicrobial susceptibility and growth-phase-dependent regulation, laying groundwork for future studies of species-specific host–microbe interactions in the gut.
2026-04-27 | PXD074583 | Pride
Project description:Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on hepatic lipid metabolism and detailed serum lipid profiles, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to measure quantitatively serum lipid profiles and whole genome microarray analysis was used to identify the responsible mechanisms in liver. There were no significant differences found in mean body weight, energy intake and hepatic lipid accumulation between the quercetin and control group. In serum of quercetin-fed mice, TG levels were decreased with 15%, poly unsaturated fatty acids (PUFA) were increased with 14% and saturated fatty acids were decreased. Palmitic acid, oleic acid, and linoleic acid were all decreased in quercetin-fed mice by 9-15%. Both palmitic acid and oleic acid can be oxidized by omega-oxidation. Indeed, gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially omega-oxidation. At the gene level, this was reflected by the up regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, Cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor Constitutive androstane receptor (Car; official symbol Nr1i3) were also up regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid omega-oxidation and lowered corresponding circulating lipid levels, a process that may involve Por and Car, and results in a potential beneficial CVD preventive effect. Liver samples were obtained from 36 C57BL/6J male adult mice. All mice started with a three week adaptation phase, in which they were fed a mild-high-fat diet. 12 mice were sacrificed immediately after the adaptation phase (t=0). The other 24 mice received the mild-high-fat diet without (HF) or with supplementation of 0.33% (w/w) quercetin (HF-Q) for 12 weeks.
2013-02-05 | E-GEOD-39140 | biostudies-arrayexpress
Project description:Elevated circulating lipid levels are known risk factors for cardiovascular diseases (CVD). In order to examine the effects of quercetin on hepatic lipid metabolism and detailed serum lipid profiles, mice received a mild-high-fat diet without (control) or with supplementation of 0.33% (w/w) quercetin for 12 weeks. Gas chromatography and 1H nuclear magnetic resonance were used to measure quantitatively serum lipid profiles and whole genome microarray analysis was used to identify the responsible mechanisms in liver. There were no significant differences found in mean body weight, energy intake and hepatic lipid accumulation between the quercetin and control group. In serum of quercetin-fed mice, TG levels were decreased with 15%, poly unsaturated fatty acids (PUFA) were increased with 14% and saturated fatty acids were decreased. Palmitic acid, oleic acid, and linoleic acid were all decreased in quercetin-fed mice by 9-15%. Both palmitic acid and oleic acid can be oxidized by omega-oxidation. Indeed, gene expression profiling showed that quercetin increased hepatic lipid metabolism, especially omega-oxidation. At the gene level, this was reflected by the up regulation of cytochrome P450 (Cyp) 4a10, Cyp4a14, Cyp4a31 and Acyl-CoA thioesterase 3 (Acot3). Two relevant regulators, Cytochrome P450 oxidoreductase (Por, rate limiting for cytochrome P450s) and the transcription factor Constitutive androstane receptor (Car; official symbol Nr1i3) were also up regulated in the quercetin-fed mice. We conclude that quercetin intake increased hepatic lipid omega-oxidation and lowered corresponding circulating lipid levels, a process that may involve Por and Car, and results in a potential beneficial CVD preventive effect.
2013-02-05 | GSE39140 | GEO
Project description:OBJECTIVE Diet intervention in obese adults is the first strategy to induce weight loss and to improve insulin sensitivity. We hypothesized that improvements in insulin sensitivity after weight loss from a short-term dietary intervention tracks with alterations in expression of metabolic genes and abundance of specific lipid species. RESEARCH DESIGN AND METHODS Eight obese, insulin resistant, non-diabetic adults were recruited to participate in a three-week low calorie diet intervention study (1000 kcal/day). Fasting blood samples and vastus lateralis skeletal muscle biopsies were obtained before and after the dietary intervention. Clinical chemistry and measures of insulin sensitivity were determined. Unbiased microarray gene expression and targeted lipidomic analysis of skeletal muscle was performed. RESULTS Body weight was reduced, insulin sensitivity (HOMA-IR) was enhanced, and serum insulin concentration and blood lipid (triglyceride, cholesterol, LDL and HDL) levels were improved after dietary intervention. Gene set enrichment analysis of skeletal muscle revealed that oxidative phosphorylation and inflammatory processes were among the most enriched KEGG-pathways identified after dietary intervention. mRNA expression of PDK4 and MLYCD increased, while SCD decreased in skeletal muscle after dietary intervention. Dietary intervention altered the intramuscular lipid profile of skeletal muscle, with changes in content of phosphatidylcholine and triglyceride species among the pronounced. CONCLUSIONS Short-term diet intervention and weight loss in obese adults alters metabolic gene expression and reduces specific phosphatidylcholine and triglyceride species in skeletal muscle, concomitant with improvements in clinical outcomes and enhanced insulin sensitivity.
2019-02-05 | GSE103682 | GEO
Project description:Background---For decades, plasma lipid levels have been known risk factors of atherosclerosis. Recently, inflammation has gained acceptance as a crucial event in the pathogenesis and development of atherosclerosis. A number of studies have provided some insights into the relationships between the two aspects of atherosclerosis: plasma lipids --- the risk factors, and circulating leukocytes --- the effectors of inflammation. In this study, we investigate the relationships between plasma lipids and leukocytes. Methods and Results---No significant correlation was found between leukocyte counts and plasma lipid levels in 74 individuals. Profiling and analyzing the leukocyte gene expression of 32 individuals revealed distinctive patterns in response to plasma lipid levels: 1) genes involved in lipid metabolism and in the electron transport chain were positively correlated with triglycerides and low-density lipoprotein cholesterol levels, and negatively correlated with high-density lipoprotein cholesterol levels; 2) genes involved in platelet activation were negatively correlated with high-density lipoprotein cholesterol levels; 3) transcription factors regulating lipidgenesis-related genes were correlated with plasma lipid levels; 4) a number of genes correlated to plasma lipid levels were found located in the regions of known QTLs associated with hyperlipemia. Conclusions--- We discovered interesting patterns of leukocyte gene expression in response to plasma lipid levels. Most importantly, genes involved in lipid metabolism, the electron transportation chain, and platelet activation were found correlated with plasma lipid levels. We suggest that leukocytes respond to changing plasma lipid levels by regulating a network of genes, including genes involved in lipid and fatty acid metabolism, through the activation of key transcription factors, such as sterol regulatory element binding transcription factors and peroxisome proliferative activated receptors. Keywords: Atherosclerosis, leukocyte, lipid, gene expression
2006-08-04 | GSE3059 | GEO
Project description: Not available
| S-EPMC5012424 | biostudies-literature
Project description:Cholesterol constitutes ~30% of the lipids in the vertebrate cell plasma membrane (PM), where it plays indispensable roles in membrane trafficking and receptor signaling. Despite this, how PM cholesterol levels are sensed and regulated remains incompletely understood. Using a genome-wide screen we found that ACC1, the rate-limiting enzyme in fatty acid biosynthesis, is required to maintain PM cholesterol homeostasis. ACC1 loss causes a ~10-fold increase in PM cholesterol in cells and a mouse model. We find evidence that ACC1 controls PM cholesterol indirectly through regulating lipid droplet (LD) abundance. LD depletion blocks cholesterol trafficking out of the PM in unstimulated cells and in response to 25-hydroxycholesterol, an immune signaling molecule. Conversely, when LD numbers are elevated, PM cholesterol levels decrease. These findings uncover a previously unrecognized role for ACC1 and LDs in PM cholesterol regulation, which has implications for diseases where LD numbers are altered, from metabolic syndromes to neurodegeneration.
2026-05-23 | GSE298034 | GEO
Project description:Type 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid storage exceeds intracellular needs and induces lipotoxic events ultimately contributing to the development of insulin resistance. Lipid droplet (LD)-coating proteins may control proper lipid storage in skeletal muscle. Perilipin 2 (PLIN2/ADRP) is one of the most abundantly expressed LD-coating proteins in skeletal muscle. Here we examined the role of PLIN2 in myocellular lipid handling and insulin sensitivity by investigating the effects of in vitro PLIN2 knockdown and in vitro and in vivo overexpression. PLIN2 knockdown decreased LD formation and triacylglycerol storage, marginally increased FA oxidation, and increased incorporation of palmitate into diacylglycerols and phospholipids. PLIN2 overexpression in vitro increased intramyocellular TAG storage paralleled with improved insulin sensitivity. In vivo muscle-specific PLIN2 overexpression resulted in increased LD accumulation and blunted the high-fat diet-induced increase of OXPHOS protein content. Diacylglycerol levels were unchanged, while ceramide levels were increased. Despite the increased intramyocellular lipid accumulation, PLIN2 overexpression improved skeletal muscle insulin sensitivity. We conclude that PLIN2 is essential for lipid storage in skeletal muscle by enhancing the partitioning of excess FAs towards triacylglycerol storage in LDs thereby blunting lipotoxicity-associated insulin resistance. C2C12 cells (mouse myoblast cell line) were treated with fatty acids and effects of knockdown of Perilipin 2 by siRNA were studied by gene expression profiling.
2012-06-08 | E-GEOD-38590 | biostudies-arrayexpress
Project description:Background: While atopic dermatitis (AD) often starts in early childhood, detailed tissue profiling of early-onset AD in children is lacking, hindering therapeutic development for this patient population with a particularly high unmet need of better treatments. Objective: We sought to globally profile the skin of infants with AD compared to adults with AD and healthy controls. Methods: We performed microarray, RT-PCR and fluorescence microscopy studies in infants and young children (<5yo) with early-onset AD (<6mo) compared to age-matched controls and adults with longstanding AD. Results: Transcriptomic analyses revealed profound differences between early-onset pediatric vs. longstanding adult AD, not only in lesional but also non-lesional tissues. While both patient populations harbored Th2-centered inflammation, pediatric AD also showed significant Th17-skewing, but lacked the Th1 upregulation that characterizes adult AD. Defects in lipid barrier (e.g. ELOVL3, DGAT2) and tight junction regulation (e.g. Claudins 8 and 23) were evident in both groups but, unlike adult AD which showed the classic downregulation of epidermal differentiation and cornification products, pediatric AD exhibited relatively normal expression of these genes. Some lipid-associated mediators (such as FAR2 and FA2H) even showed preferential downregulation in pediatric AD, and lipid barrier genes (FA2H, DGAT2) showed inverse correlations with transepidermal water loss/TEWL, a functional measure of the epidermal barrier. Conclusions: Children and adult AD skin samples share lipid metabolism and tight junction alterations, but epidermal differentiation complex defects are only present in adult AD, potentially resulting from chronic immune aberration that is not yet present in early-onset disease.
2018-05-21 | GSE107361 | GEO