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Drosophila E78A nuclear receptor regulates intestinal dietary triacylglyceride uptake and systemic lipid levels

ABSTRACT: Drosophila E78A nuclear receptor regulates intestinal dietary triacylglyceride uptake and systemic lipid levels

PROVIDER: PRJNA638130 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11955123_1.fastq.gz	Fastqsanger.gz
	SRR11955123_2.fastq.gz	Fastqsanger.gz
	SRR11955124_1.fastq.gz	Fastqsanger.gz
	SRR11955124_2.fastq.gz	Fastqsanger.gz
	SRR11955125_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Drosophila E78A nuclear receptor regulates intestinal dietary triacylglyceride uptake and systemic lipid levels

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

Cooperation between ASTER-dependent nonvesicular transport and NPC1L1 facilitates dietary cholesterol uptake

Project description:Intestinal cholesterol absorption is an important determinant of systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1), the target of the drug ezetimibe, is a critical player in dietary cholesterol uptake. But how cholesterol moves within the cell downstream of NPC1L1 is unknown. Here we show that the nonvesicular sterol transporters Aster-B and -C cooperate with NPC1L1 to deliver dietary cholesterol from the gut lumen to the enterocyte ER for chylomicron packaging. Aster proteins are recruited to the enterocyte plasma membrane (PM) in response to NPC1L1-dependent cholesterol accumulation. Mice lacking Asters in intestine have impaired cholesterol absorption, and reduced plasma cholesterol. NanoSIMS imaging and tracer studies reveal delayed lipid trafficking into chylomicrons in Aster-deficient enterocytes. Interestingly, in addition to potently blocking NPC1L1, ezetimibe is also a low-affinity inhibitor of Aster-B and -C but not -A, and the structure of the Aster-C-ezetimibe complex reveals the basis for this selectivity. Our findings support a model in which NPC1L1 enriches dietary cholesterol at the apical PM, and ASTERs subsequently traffic this cholesterol to the ER. The findings identify the enterocyte Aster pathway as potential target for treatment of hypercholesterolemia. Alessandra Ferrari, PhD

2023-12-21 | GSE206780 | GEO

Nonvesicular sterol transport is a metabolic immune checkpoint that guards dietary lipid uptake (scRNA-Seq)

Project description:Nonvesicular sterol transport is a metabolic immune checkpoint that guards dietary lipid uptake (scRNA-Seq)

| PRJNA1160861 | ENA

Elevated dairy fat intake in lactating women alters milk lipid and fatty acids without detectible changes in expression of genes related to lipid uptake or synthesis

Project description:Previous work has demonstrated that elevated maternal lipid intake (particularly from dairy products) is associated with increased lipids and altered fatty acid profile in milk produced by healthy lactating women. We investigate our primary hypothesis that a maternal diet rich in full-fat dairy products would simultaneously increase milk lipid percent and expression of genes related to the uptake and/or de novo biosynthesis of milk lipids. Within a a randomized, crossover study we performed a microarray analysis comparing 6 lactating women with diets rich in full-fat or non-fat dairy products. Each woman consumed one of the two diets during timepoint one, and after a two week washout period, switched over to the other diet. The timepoint value indicates whether the particular dietary treatment was consumed first or second.

2015-02-24 | E-GEOD-66191 | biostudies-arrayexpress

Elevated Dietary Non-Esterified Fatty Acid Levels Impact BeWo Trophoblast Metabolism and Lipid Processing: A Multi-OMICS Outlook

Project description:Maternal obesity and gestational diabetes mellitus (GDM) are associated with adverse intrauterine environments that are high in circulating nutrients. These adverse environments facilitate impairments in placental mitochondrial function and nutrient processing that ultimately leads to an increased risk of the exposed offspring developing non-communicable cardiometabolic health disorders (e.g. obesity, type 2 diabetes, metabolic syndrome). Analysis of fasting serum lipid levels in the third trimester has highlighted that Palmitate (PA) and oleate (OA) are the most abundance non-esterified fatty acids (NEFAs) in circulation. More importantly, these important NEFAs are elevated in both obese and GDM pregnancies. As PA and OA are the most abundant NEFAs in the typical “Westernized Diet” they elevated levels in obese and GDM pregnancies may highlight increased maternal consumption of these fats and could be a link between poor diet and abberant placental function. However, the independent and combined impacts of dietary PA and OA on mitochondrial function and nutrient processing in placental trophoblast cells remains poorly defined. Thus, in this study we sought to utilize a multi-omics approach (combining transcriptomics with untargeted metabolomics and lipidomics) to elucidate the underlying impacts of elevated NEFA levels on BeWo placental trophoblast cells. We highlighted a significant enrichment in the Wikipathways Fatty Acid Biosynthesis Pathway in BeWo cytotrophoblast cells treated with a combination of PA and OA (P/O; 50 µM each). Further, we identified differential expression of genes involved in lipid processing (e.g. ACADVL, ACACB, ACSL5, CREB3L3, PLIN2, and SCD) in BeWo cytotrophoblast cells treated with dietary NEFA species. Overall, these data highlighted that alterations in lipid processing, storage, and oxidation are implicated in the development of placental dysfunction in response to elevated lipid levels.

2023-08-30 | GSE197385 | GEO

Dietary titanium dioxide (E171) increases systemic ROS levels and alters the colon transcriptome – Evidence from a human dietary intervention study

Project description:Dietary titanium dioxide (E171) increases systemic ROS levels and alters the colon transcriptome – Evidence from a human dietary intervention study

| PRJEB88897 | ENA

The Drosophila E78 nuclear receptor regulates dietary triglyceride uptake and systemic lipid levels.

Project description:BackgroundLipid levels are maintained by balancing lipid uptake, synthesis, and mobilization. Although many studies have focused on the control of lipid synthesis and mobilization, less is known about the regulation of lipid digestion and uptake.ResultsHere we show that the Drosophila E78A nuclear receptor plays a central role in intestinal lipid homeostasis through regulation of the CG17192 digestive lipase. E78A mutant adults fail to maintain proper systemic lipid levels following eclosion, with this effect largely restricted to the intestine. Transcriptional profiling by RNA-seq revealed a candidate gene for mediating this effect, encoding the predicted adult intestinal lipase CG17192. Intestine-specific disruption of CG17192 results in reduced lipid levels similar to that seen in E78A mutants. In addition, dietary supplementation with free fatty acids, or intestine-specific expression of either E78A or CG17192, is sufficient to restore lipid levels in E78A mutant adults.ConclusionThese studies support the model that E78A is a central regulator of adult lipid homeostasis through its effects on CG17192 expression and lipid digestion. This work also provides new insights into the control of intestinal lipid uptake and demonstrate that nuclear receptors can play an important role in these pathways.

| S-EPMC8299869 | biostudies-literature

Restriction of essential amino acids dictates the systemic response to dietary protein dilution

Project description:Dietary protein dilution (DPD) promotes metabolic remodelling and health but the precise nutritional components driving this response remain elusive. Here we demonstrate that dietary amino acids (AA) are sufficient and necessary to drive the response to DPD. In particular, the restriction of dietary essential AA (EAA) supply, but not non-EAA, drives the systemic metabolic response to total AA deprivation. Furthermore, systemic deprivation of Thr and Trp, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Thr is also potentially limiting in low-protein diet fed humans, and dietary Thr restriction (DTR) retarded the development of obesity-associated metabolic dysfunction in mice. Liver-derived fibroblast growth factor 21 was required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of Thr biosynthetic capacity reversed the systemic response to DTR. Taken together, our studies demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.

2020-06-15 | PXD018205 | Pride

Flattened circadian glucocorticoid oscillations cause obesity due to increased lipid turnover and lipid uptake

Project description:Flattened circadian glucocorticoid oscillations cause obesity due to increased lipid turnover and lipid uptake

| PRJNA837272 | ENA

Identification of hypoxia-regulated genes in the liver of common sole (Solea solea) fed different dietary lipid contents

Project description:Hepatic transcriptome of sole fed low and high lipid dietary content in the early response to hypoxic stress. Characterization of the hepatic transcriptome of S. solea in order to assess the molecular mechanisms underlying the effects of dietary lipid content on hypoxia tolerance in common sole. S. solea individuals (8 month post-hatching) were fed for two month with commercial diets containing either 11% lipids or 20% lipids. Before hypoxia challenge stress, 38 individuals (19 from each dietary group) were randomly pooled in a single tank (1 m3) and left undisturbed and unfed for 48 h. The hypoxia challenge consisted then in a decrease of water oxygenation from 100 % to 10 % within one hour, followed by a slower descent at 2 % hr-1 to 4%. As fish lost their equilibrium, they were removed and sampled. Thirty six individuals (18 from each dietary group) were also sampled in normoxic conditions, resulting in 4 experimental groups: Normoxia low-lipid, Normoxia high-lipid, Hypoxia low-lipid, Hypoxia high-lipid. The experimental design was therefore a 2-way full factorial design between two juvenile dietary lipid contents and two oxygen concentration conditions.

2013-10-07 | E-GEOD-44579 | biostudies-arrayexpress

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