Receptor-independent actions of PPAR thiazolidinedione agonists: Is mitochondrial function the key?

Feinstein, D.L.; Spagnolo, A.; Akar, C.; Weinberg, G.; Murphy, P.; Gavrilyuk, V.; Russo, C. Dello

doi:10.1016/j.bcp.2005.03.033

Cited by 278Peroxisome Proliferator-Activated ReceptorsAdipose Tissue and MetabolismMetabolism, Diabetes, and Cancer

Receptor-independent actions of PPAR thiazolidinedione agonists: Is mitochondrial function the key?

Feinstein, D.L., Spagnolo, A., Akar, C., Weinberg, G., Murphy, P., Gavrilyuk, V., Russo, C. Dello·2005·Biochemical Pharmacology

DOI 10.1016/j.bcp.2005.03.033

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Abstract

Agonists of the peroxisome proliferator activated receptor gamma (PPAR(gamma)) are currently used for treatment of type 2 diabetes due to their insulin sensitizing and glucose metabolism stabilizing effects. More recently some of these same agonists were shown to exert anti-inflammatory and anti-proliferative effects as well. Although PPAR(gamma) agonists can operate via receptor-mediated events occurring at the genomic level, thereby causing long lasting changes in gene expression patterns, recent studies demonstrate non-genomic as well as genomic actions, and receptor-dependent as well as receptor-independent effects of the thiazolidinedione (TZD) class of PPAR(gamma) agonists. In this review we will summarize data describing some of these novel, receptor independent actions of TZDs, review evidence that TZDs directly influence mitochondrial function, and attempt to reconcile how changes in mitochondrial function could contribute to other receptor-independent actions of these drugs.

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Recently published data hint to efficacy of lanifibranor on liver histology and metabolic control independently of PNPLA3 status.
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15‐Deoxy‐Δ<sup>12,14</sup>‐prostaglandin J<sub>2</sub>regulates the functional state and the survival of microglial cells through multiple molecular mechanisms
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Inhibition of glial cell proinflammatory activities by peroxisome proliferator‐activated receptor gamma agonist confers partial protection during antimyelin oligodendrocyte glycoprotein demyelination in vitro
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From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions
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PPARγ Agonists as Therapeutics for the Treatment of Alzheimer's Disease
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Thiazolidinedione Class of Peroxisome Proliferator-Activated Receptor γ Agonists Prevents Neuronal Damage, Motor Dysfunction, Myelin Loss, Neuropathic Pain, and Inflammation after Spinal Cord Injury in Adult Rats
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Peroxisome proliferator‐activated receptor‐γ agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type‐2 diabetic rodents
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Structure–function analysis of NEET proteins uncovers their role as key regulators of iron and ROS homeostasis in health and disease
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The PPAR-γ agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys
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The Outer Mitochondrial Membrane Protein mitoNEET Contains a Novel Redox-active 2Fe-2S Cluster
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The Role of Peroxisome Proliferator-Activated Receptor-γ (PPARγ) in Alzheimer’s Disease
Jiang, Q., Heneka, M. T., & Landreth, G. E. (2008) · CNS Drugs · doi:10.2165/00023210-200822010-00001 · Cited by 174 · see citing works
Identification of a mitochondrial target of thiazolidinedione insulin sensitizers (mTOT)—relationship to newly identified mitochondrial pyruvate carrier proteins
Colca, J. R., McDonald, W. G., Cavey, G. S., Cole, S. L., Holewa, D. D., Brightwell-Conrad, A. S., Wolfe, C. L., Wheeler, J. S., Coulter, K. R., Kilkuskie, P. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061551 · Cited by 171 · see citing works
The PPARγ Agonist Pioglitazone Ameliorates Aging-Related Progressive Renal Injury
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Interference with PPARγ Function in Smooth Muscle Causes Vascular Dysfunction and Hypertension
Halabi, C. M., Beyer, A., de Lange, W. J., Keen, H. L., Baumbach, G. L., Faraci, F. M., & Sigmund, C. D. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.12.008 · Cited by 166 · see citing works
Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease?
Huttasch, M., Roden, M., & Kahl, S. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155937 · Cited by 169 · see citing works
PPAR: a therapeutic target in Parkinson’s disease
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Rosiglitazone decreases peroxisome proliferator receptor-gamma levels in microglia and inhibits TNF-alpha production: new evidences on neuroprotection in a progressive Parkinson's disease model
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Crystal structure of human mitoNEET reveals distinct groups of iron–sulfur proteins
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Authors: Feinstein, D. L., Spagnolo, A., Akar, C., Weinberg, G., Murphy, P., Gavrilyuk, V., & Russo, C. D.
Affiliations: University of Illinois Chicago (US)
Corresponding author: Feinstein, D.L.
ORCID: Feinstein, D.L.
Spagnolo, A.
Russo, C. Dello
Venue: Biochemical Pharmacology
Publisher: Elsevier BV
Published: 2005-07
Volume: 70
Issue: 2
Pages: 177-188
ISSN: 0006-2952 (ISSN-L)
DOI: 10.1016/j.bcp.2005.03.033
OpenAlex: W2088356767
Cited by: 275
References: 143
Citations by year: 2026: 3 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 8 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 13 · 2014: 19 · 2013: 17 · 2012: 19
FWCI: 2.37
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biochemical Pharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: PPARγ agonists, thiazolidinediones, non-genomic signaling, mitochondrial function, type 2 diabetes, insulin sensitization, anti-inflammatory activity, antiproliferative activity
MeSH terms: Animals, Humans, Mitochondria, Thiazolidinediones, PPAR gamma

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Receptor-independent actions of PPAR thiazolidinedione agonists: Is mitochondrial function the key?

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