scholarly journals Assessment of Chitosan-Affected Metabolic Response by Peroxisome Proliferator-Activated Receptor Bioluminescent Imaging-Guided Transcriptomic Analysis

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e34969 ◽  
Author(s):  
Chia-Hung Kao ◽  
Chien-Yun Hsiang ◽  
Tin-Yun Ho
Keyword(s):  
Metabolic Response ◽  
Transcriptomic Analysis ◽  
Bioluminescent Imaging ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Changes in PGC-1α-Dependent Mitochondrial Biogenesis Are Associated with Inflexible Hepatic Energy Metabolism in the Offspring Born to Dexamethasone-Treated Mothers

Livers ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 201-220
Author(s):  
Carolina Vieira Campos ◽  
Caio Jordão Teixeira ◽  
Tanyara Baliani Payolla ◽  
Amanda Rabello Crisma ◽  
Gilson Masahiro Murata ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Biogenesis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Metabolic Response ◽  
In Utero ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Energy Metabolism ◽  
Neonatal Liver ◽  
Tag Accumulation

In the present study we investigated the participation of hepatic peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) in the metabolic programming of newborn rats exposed in utero to dexamethasone (DEX). On the 21st day of life, fasted offspring born to DEX-treated mothers displayed increased conversion of pyruvate into glucose with simultaneous upregulation of PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose-6-phosphatase). Increased oxidative phosphorylation, higher ATP/ADP ratio and mitochondrial biogenesis and lower pyruvate levels were also found in the progeny of DEX-treated mothers. On the other hand, the 21-day-old progeny of DEX-treated mothers had increased hepatic triglycerides (TAG) and lower CPT-1 activity when subjected to short-term fasting. At the mechanistic level, rats exposed in utero to DEX exhibited increased hepatic PGC-1α protein content with lower miR-29a-c expression. Increased PGC-1α content was concurrent with increased association to HNF-4α and NRF1 and reduced PPARα expression. The data presented herein reveal that changes in the transcription machinery in neonatal liver of rats born to DEX-treated mothers leads to an inflexible metabolic response to fasting. Such programming is hallmarked by increased oxidative phosphorylation of pyruvate with impaired FFA oxidation and hepatic TAG accumulation.

scholarly journals The Role of GPR109a Signaling in Niacin Induced Effects on Fed and Fasted Hepatic Metabolism

2021 ◽  
Vol 22 (8) ◽  
pp. 4001
Author(s):  
Caroline E. Geisler ◽  
Kendra E. Miller ◽  
Susma Ghimire ◽  
Benjamin J. Renquist
Keyword(s):  
Knockout Mice ◽  
Metabolic Response ◽  
Regulatory Element ◽  
Apolipoprotein A1 ◽  
Peroxisome Proliferator ◽  
Fasting Serum ◽  
Endogenous Ligand ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fed State ◽  
Triglyceride Accumulation

Signaling through GPR109a, the putative receptor for the endogenous ligand β-OH butyrate, inhibits adipose tissue lipolysis. Niacin, an anti-atherosclerotic drug that can induce insulin resistance, activates GPR109a at nM concentrations. GPR109a is not essential for niacin to improve serum lipid profiles. To better understand the involvement of GPR109a signaling in regulating glucose and lipid metabolism, we treated GPR109a wild-type (+/+) and knockout (−/−) mice with repeated overnight injections of saline or niacin in physiological states characterized by low (ad libitum fed) or high (16 h fasted) concentrations of the endogenous ligand, β-OH butyrate. In the fed state, niacin increased expression of apolipoprotein-A1 mRNA and decreased sterol regulatory element-binding protein 1 mRNA independent of genotype, suggesting a possible GPR109a independent mechanism by which niacin increases high-density lipoprotein (HDL) production and limits transcriptional upregulation of lipogenic genes. Niacin decreased fasting serum non-esterified fatty acid concentrations in both GPR109a +/+ and −/− mice. Independent of GPR109a expression, niacin blunted fast-induced hepatic triglyceride accumulation and peroxisome proliferator-activated receptor α mRNA expression. Although unaffected by niacin treatment, fasting serum HDL concentrations were lower in GPR109a knockout mice. Surprisingly, GPR109a knockout did not affect glucose or lipid homeostasis or hepatic gene expression in either fed or fasted mice. In turn, GPR109a does not appear to be essential for the metabolic response to the fasting ketogenic state or the acute effects of niacin.

scholarly journals PPAR control: it's SIRTainly as easy as PGC

2009 ◽  
Vol 204 (2) ◽  
pp. 93-104 ◽  
Author(s):  
Mary C Sugden ◽  
Paul W Caton ◽  
Mark J Holness
Keyword(s):  
Metabolic Response ◽  
Common Mechanism ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Regulatory Interactions ◽  
Recent Advances ◽  
Expression Of Genes ◽  
Lipin 1 ◽  
Regulatory Loop

This review describes recent advances in our knowledge of the regulatory interactions influencing the expression of peroxisome proliferator-activated receptor (PPAR)-regulated genes. We address recent advances highlighting the role of PPARγ (PPARG) coactivator-1 (PGC-1) and lipin-1 in co-ordinating the expression of genes controlling nutrient handling. We evaluate the possibility that SIRT1 lies at the heart of a regulatory loop involving PPARα, PGC-1α (PPARA, PPARGC1A as given in the HUGO Database), and lipin-1 (LPIN1 as listed in the HUGO Database) that ultimately controls the metabolic response to varying nutrient and physiological signals via a common mechanism mediated by post-translation modifications (deacetylation) of both PPARα and PGC-1s. Finally, we comment on the potential of pharmaceutical manipulation of these targets as well as the possible problems associated with this strategy.

scholarly journals Effects of EHP-101 on inflammation and remyelination in murine models of Multiple Sclerosis

2020 ◽  
Author(s):  
Carmen Navarrete ◽  
Adela García-Martin ◽  
Martín Garrido-Rodriguez ◽  
Leyre Mestre ◽  
Ana Feliu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Transcriptomic Analysis ◽  
Drug Candidate ◽  
Peroxisome Proliferator ◽  
Murine Models ◽  
Preclinical Models ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Brain

Abstract Background: Multiple Sclerosis (MS) is characterized by a combination of inflammatory and neurodegenerative processes in the spinal cord and the brain. Natural and synthetic cannabinoids such as VCE-004.8 have been studied in preclinical models of MS and represent promising candidates for drug development. VCE-004.8 is a multitarget synthetic cannabidiol (CBD) derivative acting as a dual Peroxisome proliferator-activated receptor-gamma/ Cannabinoid receptor type 2 (PPAR γ /CB 2) ligand agonist that also activates the Hypoxia-inducible factor (HIF) pathway. EHP-101 is an oral lipidic formulation of VCE-004.8 that has shown efficacy in several preclinical models of autoimmune, inflammatory, fibrotic and neurodegenerative diseases. Methods: The efficacy of EHP-101 in vivo was evaluated in two murine models of MS, the experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination models. In EAE, transcriptomic analysis was performed by RNA-Seq and qPCR, and inflammatory and myelination markers were detected by immunohistochemistry (IHC) and confocal microscopy in both models of MS. Results: EHP-101 alleviated clinical symptomatology in EAE and transcriptomic analysis demonstrated that EHP-101 prevented the expression of many inflammatory genes closely associated with MS pathophysiology in the spinal cord. EHP-101 normalized the expression of several genes associated with oligodendrocyte function such as Teneurin 4 (Tenm4) and Gap junction gamma-3 (Gjc3) that were downregulated in EAE. EHP-101 treatment prevented microglia activation and demyelination in both the spinal cord and the brain. Moreover, EAE was associated with a loss in the expression of Oligodendrocyte transcription factor 2 (Olig2) in the corpus callosum, a marker for oligodendrocyte differentiation, which was restored by EHP-101 treatment. In addition, EHP-101 enhanced the expression of glutathione S-transferase pi (GSTpi), a marker for mature oligodendrocytes in the brain. We also found that a diet containing 0.2 % cuprizone for six weeks induced a clear loss of myelin in the brain measured by Cryomyelin staining and Myelin basic protein (MBP) expression. Moreover, EHP-101 also prevented cuprizone-induced microglial activation, astrogliosis and reduced axonal damage. Conclusions: Our results provide evidence that EHP-101 showed potent anti-inflammatory activity, prevented demyelination and enhanced remyelination. Therefore, EHP-101 represents a promising drug candidate for the potential treatment of different forms of MS.

scholarly journals The Role of GPR109a Signaling in Niacin Induced Effects on Fed and Fasted Hepatic Metabolism

2020 ◽  
Author(s):  
Caroline Geisler ◽  
Benjamin Renquist
Keyword(s):  
Metabolic Response ◽  
Hepatic Metabolism ◽  
Peroxisome Proliferator ◽  
Endogenous Ligand ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fed State ◽  
Induce Insulin Resistance ◽  
Glucose And Lipid Metabolism ◽  
Putative Receptor ◽  
Triglyceride Accumulation

Signaling through GPR109a, the putative receptor for the endogenous ligand β-OH butyrate, inhibits adipose tissue lipolysis. Niacin, an anti-atherosclerotic drug that can induce insulin resistance, activates GPR109a at nM concentrations. GPR109a is not essential for niacin to improve serum lipid profiles. To better understand the involvement of GPR109a signaling in regulating glucose and lipid metabolism, we treated GPR109a wildtype (+/+) and knockout (-/-) mice with repeated overnight injections of saline or niacin in physiological states characterized by low (ad libitum fed) or high (16h fasted) concentrations of the endogenous ligand, β-OH butyrate. In the fed state, niacin increased expression of PEPCK mRNA independent of genotype, while increasing CPT1 mRNA only in GPR109a -/- mice. Niacin decreased fasting serum non-esterified fatty acid concentrations in both GPR109a +/+ and -/- mice. Independent of GPR109a expression, niacin blunted fast-induced hepatic triglyceride accumulation and peroxisome proliferator activated receptor α (PPARα) mRNA expression. Surprisingly, GPR109a knockout did not affect glucose or lipid homeostasis or hepatic gene expression in either fed or fasted mice. In turn, GPR109a does not appear to be essential for the metabolic response to the ketogenic state or the pharmacological benefits associated with niacin.

Protein synthesis and the expression of growth-related genes are altered by running in human vastus lateralis and soleus muscles

2009 ◽  
Vol 296 (3) ◽  
pp. R708-R714 ◽  
Author(s):  
Matthew P. Harber ◽  
Justin D. Crane ◽  
Jared M. Dickinson ◽  
Bozena Jemiolo ◽  
Ulrika Raue ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Metabolic Response ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Vastus Lateralis ◽  
Muscle Growth ◽  
Ring Finger ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Before And After

Recent evidence suggests aerobic exercise may help preserve soleus muscle mass during unloading. The purpose of this investigation was to examine the muscle-specific metabolic response to running as it relates to muscle growth. Mixed-muscle protein synthesis [fractional synthetic rate (FSR)] and gene expression (GE) were examined in the vastus lateralis (VL) and soleus (SOL) muscles from eight men (26 ± 2 yr; V̇o2max 63 ± 2 ml·kg−1·min−1) before and after a 45-min level-grade treadmill run at 77 ± 1% intensity. Muscle glycogen utilization was similar between muscles. Resting FSR was similar between the VL (0.080 ± 0.007 %/h) and SOL (0.086 ± 0.008 %/h) and was higher ( P < 0.05) 24 h postexercise compared with rest for both muscles. The absolute change in FSR was not different between muscles (0.030 ± 0.007 vs. 0.037 ± 0.012 %/h for VL and SOL). At baseline, myostatin GE was approximately twofold higher ( P < 0.05) in SOL compared with VL, while no other muscle-specific differences in GE were present. After running, myostatin GE was suppressed ( P < 0.05) in both muscles at 4 h and was higher ( P < 0.05) than baseline at 24 h for VL only. Muscle regulatory factor 4 mRNA was elevated ( P < 0.05) at 4 h in both SOL and VL; MyoD and peroxisome-proliferator-activated receptor-gamma coactivator-1α (PGC-1α) were higher ( P < 0.05) at 4 h, and forkhead box [FOXO]3A was higher at 24 h in SOL only, while muscle-RING-finger protein-1 (MuRF-1) was higher ( P < 0.05) at 4 h in VL only. Myogenin and atrogin-1 GE were unaltered. The similar increases between muscles in FSR support running as part of the exercise countermeasure to preserve soleus mass during unloading. The subtle differences in GE suggest a potential mechanism for muscle-specific adaptations to chronic run training.

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