Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways [I]

ABSTRACT: Disruption of iron metabolism is closely related to metabolic diseases. Iron deficiency is frequently associated with obesity and hepatic steatosis. However, the effects of iron supplementation on obesity and energy metabolism remain unclear. Here we show that a high-fat diet supplemented with iron reduces body weight gain and hepatic lipid accumulation in mice. Iron supplementation was found to reduce mitochondrial morphological abnormalities and upregulate gene transcription involved in mitochondrial function and beta oxidation in the liver and skeletal muscle. In both these tissues, iron supplementation increased the expression of genes involved in heme or iron–sulfur (Fe–S) cluster synthesis. Heme and Fe–S cluster, which are iron prosthetic groups contained in electron transport chain complex subunits, are essential for mitochondrial respiration. The findings of this study demonstrated that iron regulates mitochondrial signaling pathways—gene transcription of mitochondrial component molecules synthesis and their energy metabolism. Overall, the study elucidates the molecular basis underlying the relationship between iron supplementation and obesity and hepatic steatosis progression, and the role of iron as a signaling molecule.

ORGANISM(S): Mus musculus

PROVIDER: GSE161644 | GEO | 2021/05/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways [II]

Project description:Disruption of iron metabolism is closely related to metabolic diseases. Iron deficiency is frequently associated with obesity and hepatic steatosis. However, the effects of iron supplementation on obesity and energy metabolism remain unclear. Here we show that a high-fat diet supplemented with iron reduces body weight gain and hepatic lipid accumulation in mice. Iron supplementation was found to reduce mitochondrial morphological abnormalities and upregulate gene transcription involved in mitochondrial function and beta oxidation in the liver and skeletal muscle. In both these tissues, iron supplementation increased the expression of genes involved in heme or iron–sulfur (Fe–S) cluster synthesis. Heme and Fe–S cluster, which are iron prosthetic groups contained in electron transport chain complex subunits, are essential for mitochondrial respiration. The findings of this study demonstrated that iron regulates mitochondrial signaling pathways—gene transcription of mitochondrial component molecules synthesis and their energy metabolism. Overall, the study elucidates the molecular basis underlying the relationship between iron supplementation and obesity and hepatic steatosis progression, and the role of iron as a signaling molecule.

2021-05-24 | GSE161646 | GEO

Obesity, Iron Regulation and Colorectal Cancer Risk

Project description:Obesity is an independent risk factor for colorectal cancer (CRC) although the underlying mechanisms have not been elucidated. Dietary nutrients play a key role in both the prevention and promotion of CRC. While iron is an essential nutrient, excess iron is associated with carcinogenesis. Unlike the systemic compartment, the intestinal lumen lacks an efficient system to regulate iron. In conditions when dietary iron malabsorption and intestinal inflammation co-exist, greater luminal iron is associated with increased intestinal inflammation and a shift in the gut microbiota to more pro-inflammatory strains. However, treatments designed to reduce luminal, including diet restriction and chelation, are associated with lower intestinal inflammation and the colonization of protective gut microbes. Obesity is associated with inflammation-induced, hepcidin-mediated, iron metabolism dysfunction characterized by iron deficiency and dietary iron malabsorption. Obesity is also linked to intestinal inflammation. Currently, there is a fundamental gap in understanding how altered iron metabolism impacts CRC risk in obesity. The investigator’s objective is to conduct a crossover controlled feeding trial of: 1) a "Typical American" diet with "high" heme/non-heme iron", 2) a "Typical American" diet with "low" iron, and 3) a Mediterranean diet with "high" non heme iron and examine effects on colonic and systemic inflammation and the gut microbiome.

| 2274754 | ecrin-mdr-crc

Translatomics probes into the role of lycopene on improving hepatic steatosis induced by high-fat diet

Project description:Liver is an important organ for fat metabolism. Excessive intake of a high-fat/energy diet is a major cause of hepatic steatosis and its complications such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Supplementation with lycopene, a natural compound, is effective in lowering triglyceride levels in the liver, although the underlying mechanism at the translational level is unclear. In this study, mice were fed a high-fat diet (HFD) to induce hepatic steatosis and treated with or without lycopene. Translation omics and transcriptome sequencing were performed on the liver to explore the regulatory mechanism of lycopene in liver steatosis induced by HFD, and identify differentially expressed genes (DEGs).

2021-06-17 | GSE178322 | GEO

Proteomics analysis of rat liver after disulfiram treatment

Project description:Obesity has become a global health concern. A molecule that safely prevents and/or treats obesity is urgently needed. Here, we show that long-term diet supplementation of disulfiram (DSF, Antabuse®), an FDA-approved drug, abrogated the adverse impact of an obesogenic diet on insulin responsiveness, while mitigating liver steatosis, cardiovascular remodeling, and pancreatic islet hypertrophy in mice. Additionally, DSF treatment of already obese male and female mice reversed weight gain and alleviated metabolic dysfunctions. Loss of fat tissue and increase in liver fenestrations were also observed in rats on DSF. Transcriptomics and proteomics analyses of mouse and rat livers unveiled comparable signatures, as revealed by pathways associated with lipid and energy metabolism, redox, and detoxification. Mechanistically, markers of hepatic oxidative stress were abrogated in DSF-treated mice through activation of ALDH2 and GST activities in vivo and stimulation of autophagic flux in vitro. Thus, repurposing DSF may represent a new strategy to combat obesity and reverse the associated metabolic disorders in human.

2020-05-15 | PXD016793 | Pride

Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways [II]

Project description:Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways [II]

| PRJNA678987 | ENA

Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways [I]

Project description:Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways [I]

| PRJNA678988 | ENA

Protection from obesity and diabetes by blockade of TGF-beta/Smad3 signaling

Project description:Imbalances in glucose and energy homeostasis are at the core of the worldwide epidemic of obesity and diabetes. Here, we illustrate an important role of the TGF-beta/Smad3 signaling pathway in regulating glucose and energy homeostasis. Smad3 deficient mice are protected from diet-induced obesity and diabetes. Interestingly, the metabolic protection is accompanied by Smad3-/- white adipose tissue acquiring the bioenergetic and gene expression profile of brown fat/skeletal muscle. Smad3-/- adipocytes demonstrate a marked increase in mitochondrial biogenesis, with a corresponding increase in basal respiration, and Smad3 acts as a repressor of PGC-alpha1 expression. We observe significant correlation between TGF-beta1 levels and adiposity in rodents and humans. Further, systemic blockade of TGF-beta1 signaling protects mice from obesity, diabetes and hepatic steatosis. Together, these results demonstrate that TGF-beta signaling regulates glucose tolerance and energy homeostasis and suggest that modulation of TGF-beta1 activity might be an effective treatment strategy for obesity and diabetes. Smad3-/- and WT mice were fed with regular diet (RD) and high fat diet (HFD), and diet induced obese (DIO) mice were treated with IgG and anti-TGF-b1 antibody

2011-07-12 | E-GEOD-28598 | biostudies-arrayexpress

Oral combined contraceptives induce liver mitochondrial ROS and whole body metabolic adaptations in female mice.

Project description:Compared to age-matched men, pre-menopausal women are protected against cardiovascular disease (CVD), hepatic steatosis, diabetes, and obesity - findings that are widely attributed to estrogen action. However pre-menopausal women who use oral combined contraceptives (OC) have 2-fold higher risk of cardiovascular disease (CVD), and OC use compounds with metabolic risk factors such as dyslipidemia, hypertension, or diabetes to further increase CVD susceptibility. While mitochondrial function in metabolically important tissues such as the liver and skeletal muscle is an emerging mechanism by which estrogen may confer its protection, effects of OC use on mitochondrial function and whole body metabolism in the context of disease risk has not yet been explored. To answer this question, female C57Bl/6J mice were fed a high fat diet and treated with vehicle or OCs for 3, 12, or 20 weeks (n=6-12 per group). Liver and skeletal muscle mitochondrial function (respiratory capacity, H2O2, coupling) was measured along with clinical outcomes of cardiometabolic disease such as obesity, glucose tolerance, hepatic steatosis, and aortic atherosclerosis. Main findings include that regardless of duration of treatment, OCs induced robust increases in hepatic mitochondrial H2O2, likely due to diminished antioxidant capacity. Furthermore, OC use in female mice decreased wheel running, spontaneous physical activity, and total energy expenditure. Surprisingly, in the chronic studies (12, 20 wk) OC treated mice had lower adiposity and hepatic triglyceride content compared to control mice. Together, these studies describe tissue-specific effects of OC use on mitochondrial function as well as variable impacts on markers of metabolic disease susceptibility.

2023-09-01 | GSE214290 | GEO

Raw data for manuscript : "Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD"

Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one third of the global population. Understanding metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demonstrated that increased serine synthesis from glycine via reverse serine hydroxymethyltransferase (SHMT) is the underlying cause for decreased glycine in steatotic livers. Consequently, limited glycine availability in steatotic livers impaired glutathione synthesis under acetaminophen-induced oxidative stress, enhancing acute hepatotoxicity. Glycine supplementation or hepatocyte-specific ablation of the mitochondrial SHMT2 isoform in mice with hepatic steatosis mitigated acetaminophen-induced hepatotoxicity by supporting de novo glutathione synthesis. Thus, early metabolic changes in MASLD that limit glycine availability sensitize mice to xenobiotics even at the reversible stage of this disease.

2023-12-12 | MSV000093653 | MassIVE

Lrpprc deficiency in brown adipocytes diminishes cold-induced thermogenesis but improves systemic metabolism

Project description:Insufficient mitochondrial quantity in brown adipose tissue (BAT) causes defective thermogenesis and positive energy balance, which is coupled with the development of obesity. Whether disturbance of mitochondrial quality affects BAT function remains unknown. Here, we describe that the brown adipocyte-specific Leucine-rich PPR motif-containing protein knockout mice (LrpprcBKO) exhibited mitochondrial electron transport chain (ETC) proteome imbalance and a complete loss of the -adrenergic-stimulated thermogenesis at room temperature (RT), due to specific reduction of mtDNA-encoded genes. However, the LrpprcBKO mice were lean at normal chow and were protected against high-fat-diet-induced metabolic abnormalities, such as obesity, insulin resistance, adipose inflammation, hepatic steatosis, and hypertriglyceridemia. The beige adipocytes in inguinal white adipose tissue were expanded in LrpprcBKO mice at RT, but not at thermoneutrality. However, BAT thermogenic defects and metabolic benefits were present in LrpprcBKO mice regardless of ambient temperatures. Collectively, our results reveal that a thermogenesis-incapable BAT with mitochondrial ETC proteome imbalance can improve systemic metabolism, suggesting BAT’s contributions to thermoregulation and systemic metabolism can be uncoupled.

2021-10-07 | PXD008798 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data