BMP-dependent mobilization of fatty acid metabolism promotes Caenorhabditis elegans survival on a bacterial pathogen
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE291387 | GEO | 2025/03/12
REPOSITORIES: GEO
Similar Datasets
Project description:BMP-dependent mobilization of fatty acid metabolism promotes Caenorhabditis elegans survival on a bacterial pathogen
| PRJNA1233282 | ENA
Project description:Myostatin is a negative regulator of muscle growth and metabolism and its inhibition in mice improves insulin sensitivity, increases glucose uptake into skeletal muscle, and decreases total body fat. A recently described mammalian protein called Mss51 is significantly downregulated with myostatin inhibition. In vitro disruption of Mss51 results in increased levels of ATP, β-oxidation, glycolysis and oxidative phosphorylation. To determine the in vivo biological function of Mss51 in mice, we disrupted the Mss51 gene by CRISPR/Cas9 and found that Mss51 KO mice have normal muscle weights and fiber-type distribution but reduced fat pads. Myofibers isolated from Mss51 KO mice showed an increased oxygen consumption rate compared to WT controls, indicating an accelerated rate of skeletal muscle metabolism. The expression of genes related to oxidative phosphorylation and fatty acid β-oxidation were enhanced in skeletal muscle of Mss51 KO mice compared to that of WT mice. We found that mice lacking Mss51 and challenged with a high fat diet were resistant to diet-induced weight gain, had increased whole-body glucose turnover and glycolysis rate, and increased systemic insulin sensitivity and fatty acid β-oxidation. These findings demonstrate that Mss51 modulates skeletal muscle mitochondrial respiration and regulates whole-body glucose and fatty acid metabolism, making it a potential target for obesity and diabetes.
2019-12-31 | GSE134519 | GEO
Project description:The Wnt/Wingless signaling pathway plays critical roles in metazoan development and energy metabolism, but its involvement in lipid mobilization has remained unclear. Here, we report that canonical Wnt/Wg signaling reduces lipid accumulation in both larval and adult adipocytes, as well as cultured S2R+ cells, in Drosophila. This reduction occurs through promoting lipolysis while concurrently repressing lipogenesis and fatty acid β-oxidation. Leveraging RNA-sequencing and CUT&RUN assays, we have identified a set of Wnt target genes responsible for intracellular lipid homeostasis. Notably, active Wnt signaling directly represses the transcription of these genes, resulting in decreased triglyceride accumulation in lipid droplets, increased lipolysis, and reduced fatty acid β-oxidation. These changes lead to elevated free fatty acids and reduced triglyceride accumulation in adipocytes with active Wnt signaling. Conversely, downregulation of Wnt signaling in the fat body promotes triglyceride accumulation in both larval and adult stages. The attenuation of Wnt signaling also increases the expression of specific lipid metabolism-related genes in larval adipocytes, wing discs, and adult intestines. Collectively, our findings suggest that Wnt signaling-induced transcriptional repression plays an important role in regulating lipid homeostasis by enhancing lipolysis while simultaneously suppressing lipogenesis and fatty acid β-oxidation processes.
2024-06-18 | GSE264356 | GEO
Project description:Dietary restriction (DR) is a robust environmental intervention that slows aging in various species. Changes in fat content have been associated with DR, but whether they play a causal role in mediating various responses to DR remains unknown. We demonstrate that upon DR, Drosophila melanogaster shift their metabolism towards increasing both fatty acid synthesis and breakdown. Inhibition of acetyl CoA carboxylase (ACC), a critical enzyme in fatty acid synthesis, or fatty acid oxidation genes specifically in the muscle tissue inhibited the lifespan extension observed upon DR, suggesting a critical role for intra-myocellular fatty acid metabolism. DR enhances spontaneous activity of flies which was found to be dependent on the enhanced fatty acid metabolism. Furthermore, this increase in activity upon DR was found to partially mediate the lifespan extension upon DR. Over-expression of adipokinetic hormone (dAKH) in whole flies, which increases fat metabolism, led to an increase in spontaneous activity and lifespan in a nutrient dependent manner. Together these results suggest that in Drosophila melanogaster enhanced fat metabolism in the muscle is a key metabolic adaptation in response to DR. 24 experimental samples were analyzed using Nimblegen oligo microarrays. Wild type samples (AL without RU486) were used as the Cy3 reference/control for all experimetal comparisons.
2012-06-14 | E-GEOD-37537 | biostudies-arrayexpress
Project description:vanEunen2013 - Network dynamics of fatty acid β-oxidation (steady-state model)
Lipid metabolism plays an important role in the development of metabolic syndrome, a major risk factor for cardiovascular disease and diabetes. This model gives insights into the response of lipid oxidation to dietart and medical interventions. The model predicts the rate of lipid oxidation and the time course of most acyl carnitines. There are two models described in the paper, (i) steady-state model [ BIOMD0000000505
], (ii) time-course model [ BIOMD0000000506
]. This model corresponds to the steady-state model.
This model is described in the article:
Biochemical competition makes fatty-acid β-oxidation vulnerable to substrate overload.
van Eunen K, Simons SM, Gerding A, Bleeker A, den Besten G, Touw CM, Houten SM, Groen BK, Krab K, Reijngoud DJ, Bakker BM.
PLoS Comput Biol. 2013;9(8):e1003186.
Abstract:
Fatty-acid metabolism plays a key role in acquired and inborn metabolic diseases. To obtain insight into the network dynamics of fatty-acid β-oxidation, we constructed a detailed computational model of the pathway and subjected it to a fat overload condition. The model contains reversible and saturable enzyme-kinetic equations and experimentally determined parameters for rat-liver enzymes. It was validated by adding palmitoyl CoA or palmitoyl carnitine to isolated rat-liver mitochondria: without refitting of measured parameters, the model correctly predicted the β-oxidation flux as well as the time profiles of most acyl-carnitine concentrations. Subsequently, we simulated the condition of obesity by increasing the palmitoyl-CoA concentration. At a high concentration of palmitoyl CoA the β-oxidation became overloaded: the flux dropped and metabolites accumulated. This behavior originated from the competition between acyl CoAs of different chain lengths for a set of acyl-CoA dehydrogenases with overlapping substrate specificity. This effectively induced competitive feedforward inhibition and thereby led to accumulation of CoA-ester intermediates and depletion of free CoA (CoASH). The mitochondrial [NAD⁺]/[NADH] ratio modulated the sensitivity to substrate overload, revealing a tight interplay between regulation of β-oxidation and mitochondrial respiration.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000505
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000505 | BioModels
Project description:vanEunen2013 - Network dynamics of fatty acid β-oxidation (time-course model)
Lipid metabolism plays an important role in the development of metabolic syndrome, a major risk factor for cardiovascular disease and diabetes. This model gives insights into the response of lipid oxidation to dietart and medical interventions. The model predicts the rate of lipid oxidation and the time course of most acyl carnitines. There are two models described in the paper, (i) steady-state model [ BIOMD0000000505
], (ii) time-course model [ BIOMD0000000506
]. This model corresponds to the time-course model.
This model is described in the article:
Biochemical competition makes fatty-acid β-oxidation vulnerable to substrate overload.
van Eunen K, Simons SM, Gerding A, Bleeker A, den Besten G, Touw CM, Houten SM, Groen BK, Krab K, Reijngoud DJ, Bakker BM.
PLoS Comput Biol. 2013;9(8):e1003186.
Abstract:
Fatty-acid metabolism plays a key role in acquired and inborn metabolic diseases. To obtain insight into the network dynamics of fatty-acid β-oxidation, we constructed a detailed computational model of the pathway and subjected it to a fat overload condition. The model contains reversible and saturable enzyme-kinetic equations and experimentally determined parameters for rat-liver enzymes. It was validated by adding palmitoyl CoA or palmitoyl carnitine to isolated rat-liver mitochondria: without refitting of measured parameters, the model correctly predicted the β-oxidation flux as well as the time profiles of most acyl-carnitine concentrations. Subsequently, we simulated the condition of obesity by increasing the palmitoyl-CoA concentration. At a high concentration of palmitoyl CoA the β-oxidation became overloaded: the flux dropped and metabolites accumulated. This behavior originated from the competition between acyl CoAs of different chain lengths for a set of acyl-CoA dehydrogenases with overlapping substrate specificity. This effectively induced competitive feedforward inhibition and thereby led to accumulation of CoA-ester intermediates and depletion of free CoA (CoASH). The mitochondrial [NAD⁺]/[NADH] ratio modulated the sensitivity to substrate overload, revealing a tight interplay between regulation of β-oxidation and mitochondrial respiration.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000506
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000506 | BioModels
Project description:<p>The GOLDN study was initiated to assess how genetic factors interact with environmental (diet and drug) interventions to influence blood levels of triglycerides and other atherogenic lipid species and inflammation markers (registered at <a href="http://clinicaltrials.gov/ct2/show/NCT00083369">clinicaltrails.gov</a>, number NCT00083369). The study recruited Caucasian participants primarily from three-generational pedigrees from two NHLBI Family Heart Study (FHS) field centers (Minneapolis, MN and Salt Lake City, UT). Only families with at least two siblings were recruited and only participants who did not take lipid-lowering agents (pharmaceuticals or nutraceuticals) for at least 4 weeks prior to the initial visit were included. A total of 1048 GOLDN participants were included in the diet intervention. The diet intervention followed the protocol of Patsch et al. (<a href="http://www.ncbi.nlm.nih.gov/pubmed/1420093">1992</a>). The whipping cream (83% fat) meal had 700 Calories/m2 body surface area (2.93 MJ/m2 body surface area): 3% of calories were derived from protein (instant nonfat dry milk) and 14% from carbohydrate (sugar). The ratio of polyunsaturated to saturated fat was 0.06 and the cholesterol content of the average meal was 240 mg. The mixture was blended with ice and flavorings. Blood samples were drawn immediately before (fasting) and at 3.5 and 6 hours after consuming the high-fat meal. For the GOLDN lipidomics study, sterols and fatty acids were measured from stored plasma (-80 degrees Celsius) collected at fasting and 3.5 hours after the diet intervention using TrueMass Panels from Lipomics (West Sacramento, CA). A total of 11 sterols were quantified in nmols/gram of sample including total cholesterol, 7-dehydrocholesterol, desmosterol, lanosterol, lathasterol, cholestanol, coprostanol, beta-sitosterol, campesterol, stigmasterol, and 7alpha-hydroxycholesterol. A total of 35 fatty acids were quantified in nmols/gram of sample inlcuding myristic acid (14:0); pentadecanoic acid (15:0); palmitic acid (16:0); stearic acid (18:0); arachidic acid (20:0); behenic acid (22:0); lignoceric acid (24:0); myristoleic acid (14:1n5); palmitoleic acid (16:1n7); palmitelaidic acid (t16:1n7); oleic acid (18:1n9); elaidic acid (t18:1n9); vaccenic acid (18:1n7); linoleic acid (18:2n6); gamma-linolenic acid (18:3n6); alpha-linolenic acid (18:3n3); stearidonic acid (18:4n3); eicosenoic acid (20:1n9); eicosadienoic acid (20:2n6); mead acid (20:3n9); di-homo-gamma-linolenic acid (20:3n6); arachidonic acid (20:4n6); eicsoatetraenoic acid (20:4n3); eicosapentaenoic acid (20:5n3); erucic acid (22:1n9); docosadienoic acid (22:2n6); adrenic acid (22:4n6); docosapentaenoic acid (22:5n6); docosapentaenoic acid (22:5n3); docosahexaenoic acid (22:6n3); nervonic acid (24:1n9); and plasmalogen derivatives of 16:0, 18:0, 18:1n9, and 18:1n7.</p>
| phs000741 | dbGaP
Project description:Dietary restriction (DR) is a robust environmental intervention that slows aging in various species. Changes in fat content have been associated with DR, but whether they play a causal role in mediating various responses to DR remains unknown. We demonstrate that upon DR, Drosophila melanogaster shift their metabolism towards increasing both fatty acid synthesis and breakdown. Inhibition of acetyl CoA carboxylase (ACC), a critical enzyme in fatty acid synthesis, or fatty acid oxidation genes specifically in the muscle tissue inhibited the lifespan extension observed upon DR, suggesting a critical role for intra-myocellular fatty acid metabolism. DR enhances spontaneous activity of flies which was found to be dependent on the enhanced fatty acid metabolism. Furthermore, this increase in activity upon DR was found to partially mediate the lifespan extension upon DR. Over-expression of adipokinetic hormone (dAKH) in whole flies, which increases fat metabolism, led to an increase in spontaneous activity and lifespan in a nutrient dependent manner. Together these results suggest that in Drosophila melanogaster enhanced fat metabolism in the muscle is a key metabolic adaptation in response to DR.
2012-06-15 | GSE37537 | GEO
Project description:Energy metabolism dysfunction is highly connected with aging. Aged mice could exhibit multiple energy metabolism disorders, such as insulin resistance, inhibition of fatty acid degradation and lipid accumulation. PPARα is a key transcriptional factor regulating genes of fatty acid β-oxidation, playing a crucial role in lipid metabolism and ATP production. However, the role of PPARα in retarding organ aging has not been fully elucidated. Herein, we investigated the beneficial effects of Omega-3 PUFAs, endogenous agonists of PPARα, in naturally aging mice, accelerated aging mice as well as several kinds of cells cultures. Moreover, we performed studies in mfat-1 transgenic mice at 24 months of age to explore the anti-aging effects of Omega-3 PUFAs. We found that Omega-3 PUFAs and fat-1 gene restored fatty acid β-oxidation and ATP production, reduced lipid accumulation, inhibited age-related pathological changes, preserved organ functions to delay aging process. Our results suggest Omega-3 PUFAs is a promising therapeutic approach to promote healthy aging in the elderly.
2024-12-25 | GSE236867 | GEO
Project description:We identified differentially expressed genes in epididymal white adipose tissue of high fat diet(HFD)-fed mice compared to low fat diet-fed mice using microarray analysis. Microarray analysis revealed that genes related to lipolysis, fatty acid metabolism, mitochondrial energy transduction, oxidation-reduction, insulin sensitivity, and skeletal system development were downregulated in HFD-fed mice, and genes associated with extracellular matrix (ECM) components, ECM remodeling, and inflammation were upregulated. The top 10 up- or downregulated genes include Acsm3, mt-Nd6, Fam13a, Cyp2e1, Rgs1, and Gpnmb, whose roles in obesity-associated adipose tissue deterioration are poorly understood. Total RNA of epididymal white adipose tissue was obtained from low fat diet (10 kcal% fat)- and high fat diet(45 kcal% fat)-fed mice and mRNA expression was measured using microarray analysis.
2015-07-01 | E-GEOD-63198 | biostudies-arrayexpress