Upregulation of PPARbeta/delta is associated with structural and functional changes in the type I diabetes rat diaphragm.

PLoS One

UMRS INSERM 956, Institut de Myologie, IFR14, Université Pierre et Marie Curie-Paris 6, and Department of Emergency Medicine and Surgery, Groupe hospitalier Pitié-Salpêtrière, Assistance Publique-Hôptiaux de Paris, Paris, France.

Published: July 2010

AI Article Synopsis

  • Diabetes mellitus leads to changes in diaphragm function and muscle composition, showing a link to peroxisome proliferator-activated receptors (PPAR alpha and beta/delta) in type I diabetes.
  • In a study with streptozotocin-treated rats, diaphragmatic function was assessed, revealing a decrease in maximum velocity and myosin ATPase activity, but an increase in force and cross bridges, indicating a shift towards slow muscle fibers.
  • These adaptations were accompanied by a significant increase in PPARbeta/delta expression, suggesting potential benefits in fatigue and hypoxia resistance for diabetic subjects.

Article Abstract

Background: Diabetes mellitus is associated with alterations in peripheral striated muscles and cardiomyopathy. We examined diaphragmatic function and fiber composition and identified the role of peroxisome proliferator-activated receptors (PPAR alpha and beta/delta) as a factor involved in diaphragm muscle plasticity in response to type I diabetes.

Methodology/principal Findings: Streptozotocin-treated rats were studied after 8 weeks and compared with their controls. Diaphragmatic strips were stimulated in vitro and mechanical and energetic variables were measured, cross bridge kinetics assessed, and the effects of fatigue and hypoxia evaluated. Morphometry, myosin heavy chain isoforms, PPAR alpha and beta/delta gene and protein expression were also assessed. Diabetes induced a decrease in maximum velocity of shortening (-14%, P<0.05) associated with a decrease in myosin ATPase activity (-49%, P<0.05), and an increase in force (+20%, P<0.05) associated with an increase in the number of cross bridges (+14%, P<0.05). These modifications were in agreement with a shift towards slow myosin heavy chain fibers and were associated with an upregulation of PPARbeta/delta (+314% increase in gene and +190% increase in protein expression, P<0.05). In addition, greater resistances to fatigue and hypoxia were observed in diabetic rats.

Conclusions/significance: Type I diabetes induced complex mechanical and energetic changes in the rat diaphragm and was associated with an up-regulation of PPARbeta/delta that could improve resistance to fatigue and hypoxia and favour the shift towards slow myosin heavy chain isoforms.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900215PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011494PLOS

Publication Analysis

Top Keywords

ppar alpha
8
alpha beta/delta
8
upregulation pparbeta/delta
4
pparbeta/delta associated
4
associated structural
4
structural functional
4
functional changes
4
changes type
4
type diabetes
4
diabetes rat
4

Similar Publications

A number of studies demonstrate the therapeutic effectiveness of Radix Bupleuri (RB) and Hedysarum Multijugum Maxim (HMM) in treating liver fibrosis, but the exact molecular mechanisms remain unclear. This study aims to explore the mechanism of RB-HMM drug pairs in treating liver fibrosis by using network pharmacology, bioinformatics, molecular docking, molecular dynamics simulation technology and in vitro experiments. Totally, 155 intersection targets between RB-HMM and liver fibrosis were identified.

View Article and Find Full Text PDF

α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation.

Ecotoxicol Environ Saf

January 2025

Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China. Electronic address:

Mushroom poisoning, predominantly caused by α-amanitin, is a critical food safety concern in worldwide, with severe cases leading to hepatotoxicity and fatalities. This study delves into the hepatotoxic effects of α-amanitin, focusing on the NLRP3 inflammasome and PPAR-γ's regulatory role in inflammation. In vitro studies with L-02 cells showed that α-amanitin reduces cell viability and triggers NLRP3 inflammasome activation, increasing NF-κB phosphorylation and pro-inflammatory cytokines IL-18 and IL-1β.

View Article and Find Full Text PDF

Background: Diabetes mellitus is associated with morphological and functional impairment of the heart primarily due to lipid toxicity caused by increased fatty acid metabolism. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) have been implicated in the metabolism of fatty acids in the liver and skeletal muscles. However, their role in the heart in diabetes remains unclear.

View Article and Find Full Text PDF

L. is known in Europe for its cardioactivity-also in interrelation with known risk factors of the metabolic syndrome-just as Houtt. in East Asia; however, up to now, no active constituents could be identified.

View Article and Find Full Text PDF

Discovery of PPAR Alpha Lipid Pathway Modulators That Do Not Bind Directly to the Receptor as Potential Anti-Cancer Compounds.

Int J Mol Sci

January 2025

Medical Research Core Facility and Platforms (MRCFP)-Drug Discovery Platform, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi Arabia.

Peroxisome proliferator-activated receptors (PPARs) are considered good drug targets for breast cancer because of their involvement in fatty acid metabolism that induces cell proliferation. In this study, we used the KAIMRC1 breast cancer cell line. We showed that the PPARE-Luciferase reporter gets highly activated without adding any exogenous ligand when PPAR alpha is co-transfected, and the antagonist GW6471 can inhibit the activity.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!