Differential gene expression in the mandibular glands of queen and worker honeybees, Apis mellifera L.: Implications for caste-selective aldehyde and fatty acid metabolism

Caloric restriction (CR) increases healthy life span in a range of organisms. The underlying mechanisms are not understood but appear to include changes in gene expression, protein function, and metabolism. Recent studies demonstrate that acute CR alters mortality rates within days in flies. Multitissue transcriptional changes and concomitant metabolic responses to acute CR have not been described. We generated whole genome RNA transcript profiles in liver, skeletal muscle, colon, and hypothalamus and simultaneously measured plasma metabolites using proton nuclear magnetic resonance in mice subjected to acute CR. Liver and muscle showed increased gene expressions associated with fatty acid metabolism and a reduction in those involved in hepatic lipid biosynthesis. Glucogenic amino acids increased in plasma, and gene expression for hepatic gluconeogenesis was enhanced. Increased expression of genes for hormone-mediated signaling and decreased expression of genes involved in protein binding and development occurred in hypothalamus. Cell proliferation genes were decreased and cellular transport genes increased in colon. Acute CR captured many, but not all, hepatic transcriptional changes of long-term CR. Our findings demonstrate a clear transcriptional response across multiple tissues during acute CR, with congruent plasma metabolite changes. Liver and muscle switched gene expression away from energetically expensive biosynthetic processes toward energy conservation and utilization processes, including fatty acid metabolism and gluconeogenesis. Both muscle and colon switched gene expression away from cellular proliferation. Mice undergoing acute CR rapidly adopt many transcriptional and metabolic changes of long-term CR, suggesting that the beneficial effects of CR may require only a short-term reduction in caloric intake.

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Abstract 3: The Histone Methyltransferase Smyd1 is a Novel Transcriptional Regulator of Cardiac Fatty Acid Metabolism in Mice

Circulation Research ◽

10.1161/res.119.suppl_1.3 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Junko S Warren ◽

Dane W Barton ◽

Mickey Miller ◽

Li Wang ◽

James Cox ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Fatty Acid Metabolism ◽

Cardiac Dysfunction ◽

Acid Metabolism ◽

Transcriptional Start Site ◽

Cardiac Metabolism ◽

Histone Methyltransferase ◽

Tamoxifen Treatment ◽

Mrna Levels

Epigenetic control of metabolism in the healthy and diseased heart remains poorly understood. We recently demonstrated that chromatin-bound Smyd1, a muscle-specific histone methyltransferase, is significantly upregulated in a mouse model of pressure overload-induced heart failure (HF) and that inducible, cardiac-specific Smyd1 knock-out (Smyd1-KO) mice develop cellular hypertrophy and fulminate HF. Bioinformatic analysis of transcripts differentially regulated in these mice revealed that cardiac metabolism was the most perturbed biological function in the heart. However, it was not clear whether alterations in cardiac metabolism were a direct consequence of Smyd1 deletion or were secondary to developed HF. Here we hypothesized that Smyd1 directly regulates cardiac metabolism; the effects of which should be detectable in Smyd1-KO mice before overt cardiac dysfunction. To test this hypothesis we performed unbiased metabolomic analysis of Smyd1-KO mice using GC/MS and MS/MS (n=9 control, n=10 KO) combined with targeted gene expression analysis. Our results showed significant changes in the metabolic profile of Smyd1-KO mice at the earliest time point (3 weeks after tamoxifen treatment) in which Smyd1 protein expression was significantly reduced while cardiac function remained normal. The most profound difference, in energetics-associated pathways in these mice, was found in fatty acid β-oxidation, manifested by the decreased myocardial content of carnitine and free fatty acids and downregulation of their transporters, OCTN2 and CD36. In addition, mRNA levels of the PPAR-α complex (PPAR-α;RXR-α;PGC-1α), an established regulator of fatty acid β-oxidation, and its target genes (CPT1b;CD36;Acox1;MCAD) were significantly reduced in Smyd1-KO mice prior to the onset of cardiac dysfunction (all p<0.05). To identify whether Smyd1 directly controls gene expression of PPAR-α, we examined the PPAR-α loci using chromatin-immunoprecipitation followed by qPCR and observed significant binding of Smyd1 upstream of the PPAR-α transcriptional start site. Overall, this study identifies Smyd1 as a novel regulator of fatty acid metabolism and suggests that Smyd1 controls cardiac energetics directly by regulating gene expression of PPAR-α.

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Differential gene expression of fatty acid binding proteins during porcine adipogenesis

Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology ◽

10.1016/j.cbpb.2008.06.010 ◽

2008 ◽

Vol 151 (2) ◽

pp. 147-152 ◽

Cited By ~ 46

Author(s):

Johanna Samulin ◽

Ingunn Berget ◽

Sigbjørn Lien ◽

Hilde Sundvold

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Differential Gene Expression ◽

Binding Proteins ◽

Fatty Acid Binding Proteins ◽

Fatty Acid Binding ◽

Differential Gene

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Abstract O-1: Klf5 Regulates Cardiac Pparα and Med13 and affects Cardiac Fatty Acid Metabolism And Obesity

Circulation Research ◽

10.1161/res.115.suppl_1.o-1 ◽

2014 ◽

Vol 115 (suppl_1) ◽

Author(s):

Konstantinos Drosatos ◽

Nina Pollak ◽

Panagiotis Ntziachristos ◽

Chad M Trent ◽

Yunying Hu ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Fatty Acid Metabolism ◽

Binding Sites ◽

Transcription Initiation ◽

Acid Metabolism ◽

Gene Promoter ◽

Initiation Site ◽

White Adipocytes ◽

Metabolic Role

Krüppel-like factors (KLF) have been associated with metabolic phenotypes. Our study focused on the metabolic role of cardiac KLF5, as it showed the highest increase among all KLFs that were detected by whole genome microarrays of energy-starved hearts obtained from lipopolysaccharide (LPS)-treated mice. Analysis of ppara promoter indicated two potential binding sites for c-Jun (AP-1 sites), the transcriptional factor that is activated by LPS and reduces cardiac PPARα expression: −792/-772 bp and −719/-698 bp prior to the transcription initiation site. This analysis showed that both AP-1 sites overlap with potential KLF-binding sites. Adenovirus-mediated expression of constitutively active c-Jun in a mouse cardiomyocyte cell line (HL-1) reduced PPARα gene expression, while treatment with Ad-KLF5 had the opposite effect. Chromatin immunoprecipitation analysis (ChIP) showed that c-Jun binds both −792/-772 bp and −719/-698 sites of ppara promoter while KLF5 binds on −792/-772 bp. ChIP analysis also showed that LPS promotes c-Jun binding on −792/-772 bp, which prohibits occupation of this region by KLF5. A cardiomyocyte-specific KLF5 knockout mouse (αMHC-KLF5-/-) had normal cardiac function but reduced cardiac expression of PPARα (50%) and other fatty acid metabolism-associated genes such as CD36 (40%), LpL (20%), PGC1α (45%), AOX (28%) and Cpt1 (45%). High fat diet (HFD)-fed αMHC-KLF5-/- mice had a more profound body weight increase (35%) compared to HFD-fed WT mice (15%), as well as larger white adipocytes and brown adipocytes (H&E) and increased hepatic neutral lipid accumulation (Oil-Red-O). The obesogenic effect of cardiomyocyte-specific deletion of KLF5 resembles the phenotype of the αMHC-MED13-/- mice. We showed that KLF5 ablation reduced cardiac MED13 levels despite lack of changes in the expression levels of miR-208, a known regulator of MED13. Infection of HL-1 cells with Ad-KLF5 increased MED13 gene expression. ChIP identified a KLF5 binding site on med13 gene promoter region (-730/-714 bp). Thus, KLF5 regulates cardiac PPARα and MED13 and affects cardiac and systemic fatty acid metabolism and obesity, thus indicating KLF5 as a potential target for cardiac dysfunction associated with energetic complications, as well as for obesity

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MALDI Mass Spectrometry Imaging of Lipids and Gene Expression Reveals Differences in Fatty Acid Metabolism between Follicular Compartments in Porcine Ovaries

Biology ◽

10.3390/biology4010216 ◽

2015 ◽

Vol 4 (1) ◽

pp. 216-236 ◽

Cited By ~ 14

Author(s):

Svetlana Uzbekova ◽

Sebastien Elis ◽

Ana-Paula Teixeira-Gomes ◽

Alice Desmarchais ◽

Virginie Maillard ◽

...

Keyword(s):

Gene Expression ◽

Mass Spectrometry ◽

Fatty Acid ◽

Fatty Acid Metabolism ◽

Mass Spectrometry Imaging ◽

Acid Metabolism ◽

Maldi Mass Spectrometry ◽

Maldi Mass Spectrometry Imaging

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Global Gene Expression Profiling in PPAR-γAgonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

PPAR Research ◽

10.1155/2012/695898 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Daisuke Yoshihara ◽

Masanori Kugita ◽

Tamio Yamaguchi ◽

Harold M. Aukema ◽

Hiroki Kurahashi ◽

...

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Cell Proliferation ◽

Fatty Acid ◽

Kidney Disease ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Interstitial Fibrosis ◽

Global Gene Expression ◽

Polycystic Kidney

Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-γagonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism.

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Differential gene expression of the honey bee Apis mellifera associated with Varroa destructor infection

BMC Genomics ◽

10.1186/1471-2164-9-301 ◽

2008 ◽

Vol 9 (1) ◽

pp. 301 ◽

Cited By ~ 115

Author(s):

M Navajas ◽

A Migeon ◽

C Alaux ◽

ML Martin-Magniette ◽

GE Robinson ◽

...

Keyword(s):

Gene Expression ◽

Apis Mellifera ◽

Honey Bee ◽

Differential Gene Expression ◽

Varroa Destructor ◽

Differential Gene

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Correlation between increased atrial expression of genes related to fatty acid metabolism and autophagy in patients with chronic atrial fibrillation

10.1101/815126 ◽

2019 ◽

Author(s):

Yasushige Shingu ◽

Shingo Takada ◽

Takashi Yokota ◽

Ryosuke Shirakawa ◽

Akira Yamada ◽

...

Keyword(s):

Gene Expression ◽

Atrial Fibrillation ◽

Fatty Acid ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Right Atrial ◽

Fatty Acid Transport ◽

Acid Uptake ◽

Fatty Acid Binding ◽

Expression Of Genes

AbstractAtrial metabolic disturbance contributes to the onset and development of atrial fibrillation (AF). Autophagy plays a role in maintaining the cellular energy balance. We examined whether the altered atrial expression of genes related to fatty acid metabolism is linked to that related to autophagy in chronic AF. Right atrial tissue was obtained during heart surgery from 51 patients with sinus rhythm (SR, n=38) or chronic AF (n=13). Preoperative fasting serum free-fatty-acid levels were significantly higher in the AF patients. The atrial gene expression of fatty acid binding protein 3 (FABP3), which is involved in the cells’ fatty acid uptake and intracellular fatty acid transport, was significantly increased in AF patients compared to SR patients; in the SR patients it was positively correlated with the right atrial diameter and intra-atrial EMD, parameters of structural and electrical atrial remodeling that was evaluated by an echocardiography. In contrast, the two groups’ atrial contents of diacylglycerol (DAG), a toxic fatty acid metabolite, were comparable. Importantly, the atrial gene expression of microtubule-associated protein light chain 3 (LC3) was significantly increased in the AF patients, and autophagy-related genes including LC3 were positively correlated with the atrial expression of FABP3. In conclusion, in chronic AF patients, the atrial expression of FABP3 was upregulated in association with autophagy-related genes without altered atrial DAG content. Our findings may support the hypothesis that dysregulated cardiac fatty acid metabolism contributes to the progression of AF and induction of autophagy has a cardioprotective effect against cardiac lipotoxicity in chronic AF.

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