Early induction of a brown-like phenotype by rosiglitazone in the epicardial adipose tissue of fatty Zucker rats
Abstract
The epicardial adipose tissue (EAT) is "hypertrophied" in the obese. Thiazolidinediones are anti-diabetic, hypolipidemic drugs and are selective agonists for the gamma isoform of peroxisome proliferator-activated receptor (PPARγ). We evaluated the short-term effects of the prototype rosiglitazone (RSG, 5 mg kg(-1) day(-1) for 4 days) on the expression of the genes and proteins (by real-time PCR and Western blot) involved in fatty acid (FA) metabolism in EAT of the obese fatty Zucker rat and compared the levels of expression with those in retroperitoneal adipose tissue (RAT). The glyceroneogenic flux leading to fatty acid re-esterification was assessed by the incorporation of 14C from [1-14C]-pyruvate into neutral lipids. RSG upregulated the mRNA for phosphoenolpyruvate carboxykinase, pyruvate dehydrogenase kinase 4, glycerol kinase, adipocyte lipid binding protein, adipose tissue triglyceride lipase and lipoprotein lipase in both RAT and EAT with a resulting increase in glyceroneogenesis that, however, was more pronounced in EAT than in RAT. Under RSG, fatty acid output was decreased in both tissues but unexpectedly less so in EAT than in RAT. RSG also induced the expression of the key genes for fatty acid oxidation [carnitinepalmitoyl transferase-1, medium chain acyl dehydrogenase and very long chain acyl dehydrogenase (VLCAD)]in EAT and RAT with a resulting significant rise of the expression of VLCAD protein. In addition, the expression of the genes encoding proteins involved in mitochondrial processing and density PPARγ coactivator 1 alpha (PGC-1α), NADH dehydrogenase 1 and cytochrome oxidase (COX4) were increased by RSG treatment only in EAT, with a resulting significant up-regulation of PGC1-α and COX4 protein. This was accompanied by a rise in the expression of PR domain containing 16 and uncoupling protein 1, two brown adipose tissue-specific proteins. In conclusion, this study reveals that PPAR-γ agonist could induce a rapid browning of the EAT that probably contributes to the increase in lipid turnover.
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Rosiglitazone induces significant up-regulation of PGC1-α in obese fatty Zucker rats, responsible for rapid browning of EAT and increased lipid turnover.
“When administered to obese fatty Zucker rats, rosiglitazone induced a significant up-regulation of PGC1-α, responsible of a rapid browning of EAT and of increased rates of lipid turnover [165].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [165]
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“Treatment w ith pioglitazone was associated with a reduction of proinflammatory and anti-inflammatory genes in EAT in T2DM patients with CAD [39].”
BackgroundSalvatore, T., Galiero, R., Caturano, A., Vetrano, E., Rinaldi, L., Coviello, F., Di Martino, A., Albanese, G., Colantuoni, S., Medicamento, G., et al. (2022) · Biomolecules · doi:10.3390/biom12020176 · Cited by 62 · see citing works
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- Authors
- Distel, E., Penot, G., Cadoudal, T., Balguy, I., Durant, S., & Benelli, C.
- Affiliations
- Inserm (FR)
- Corresponding author
- Benelli, Chantal
- Venue
- Biochimie
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 94
- Issue
- 8
- Pages
- 1660-1667
- ISSN
- 0037-9042 (ISSN-L)
- 0300-9084
- OpenAlex
- W2059261716
- Cited by
- 49
- References
- 30
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 10 · 2021: 1 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 3
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimie (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministère de l'Enseignement Supérieur et de la Recherche
- Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- rosiglitazone, epicardial adipose tissue, brown adipose tissue browning, PPARγ agonists, thiazolidinediones, fatty acid metabolism, glyceroneogenesis, fatty acid oxidation, carnitine palmitoyltransferase 1, PGC-1α, UCP1, mitochondrial biogenesis, retroperitoneal adipose tissue, obesity
- MeSH terms
- Rosiglitazone, Animals, Adipose Tissue, Brown, Fatty Acids, Gene Expression Regulation, Insulin Resistance, Mitochondria, Heart, Obesity, Pericardium, Phenotype, Rats, Zucker, Thiazolidinediones, PPAR gamma, Intra-Abdominal Fat, Lipid Metabolism, Rats
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