Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Open accessAbstract
PPARalpha is a nuclear receptor that regulates liver and skeletal muscle lipid metabolism as well as glucose homeostasis. Acting as a molecular sensor of endogenous fatty acids (FAs) and their derivatives, this ligand-activated transcription factor regulates the expression of genes encoding enzymes and transport proteins controlling lipid homeostasis, thereby stimulating FA oxidation and improving lipoprotein metabolism. PPARalpha also exerts pleiotropic antiinflammatory and antiproliferative effects and prevents the proatherogenic effects of cholesterol accumulation in macrophages by stimulating cholesterol efflux. Cellular and animal models of PPARalpha help explain the clinical actions of fibrates, synthetic PPARalpha agonists used to treat dyslipidemia and reduce cardiovascular disease and its complications in patients with the metabolic syndrome. Although these preclinical studies cannot predict all of the effects of PPARalpha in humans, recent findings have revealed potential adverse effects of PPARalpha action, underlining the need for further study. This Review will focus on the mechanisms of action of PPARalpha in metabolic diseases and their associated vascular pathologies.
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PPARα is mainly found in liver and muscles.
“PPARa is mainly found in liver and muscles (Lefebvre et al., 2006).”
From The Peroxisome Proliferator–Activated Receptor (PPAR)-γ Antagonist 2-Chloro-5-Nitro-N-Phenylbenzamide (GW9662) Triggers Perilipin 2 Expression via PPARδ and Induces Lipogenesis and Triglyceride Accumulation in Human THP-1 Macrophages (2020) · cites this paper as Lefebvre et al., 2006
The “PPARα and intracellular lipid metabolism” section says PPARα is highly expressed in the liver and skeletal muscles. It also lists brown fat, heart, kidneys, and cells of atherosclerotic lesions, without saying expression is mainly in liver and muscle. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPPARα and PPARδ are related to lipid metabolism because of their key role in the regulation of fatty acid oxidation and lipoprotein metabolism.
“PPARa and PPARd are related to lipid metabolism because of their key role in the regulation of fatty acid oxidation and lipoprotein metabolism (Luquet et al., 2005;Lefebvre et al., 2006).”
From The Peroxisome Proliferator–Activated Receptor (PPAR)-γ Antagonist 2-Chloro-5-Nitro-N-Phenylbenzamide (GW9662) Triggers Perilipin 2 Expression via PPARδ and Induces Lipogenesis and Triglyceride Accumulation in Human THP-1 Macrophages (2020) · cites this paper as Lefebvre et al., 2006
The ‘PPARα and intracellular lipid metabolism’ section links PPARα to fatty acid oxidation and lipoprotein assembly and transport; the ‘Lipoprotein metabolism’ section describes its effects on lipoproteins. The copy identifies PPARδ in the Introduction but does not establish the claimed roles for PPARδ. Page numbers are unavailable in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAnti-inflammatory effects and regulatory roles in glucose metabolism have been reported for both PPARα and PPARδ.
“Furthermore, anti-inflammatory effects and regulatory roles in glucose metabolism have been reported for both isoforms (Lefebvre et al., 2006;Neels and Grimaldi, 2014;Magadum and Engel, 2018).”
From The Peroxisome Proliferator–Activated Receptor (PPAR)-γ Antagonist 2-Chloro-5-Nitro-N-Phenylbenzamide (GW9662) Triggers Perilipin 2 Expression via PPARδ and Induces Lipogenesis and Triglyceride Accumulation in Human THP-1 Macrophages (2020) · cites this paper as Lefebvre et al., 2006
The Introduction and Gene repression by PPARα sections report roles for PPARα in glucose homeostasis and anti-inflammatory effects. The Introduction links the three PPARs generally to diabetes and inflammation, but the passages do not establish both effects specifically for PPARδ. Page numbers were not provided in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPPARs are activated by a variety of molecules and act mainly as sensors for fatty acids and fatty acid-derived metabolites.
“PPARs are activated by a variety of molecules and act mainly as sensors for fatty acids and fatty acid-derived metabolites (Lefebvre et al., 2006;Tontonoz and Spiegelman, 2008;Neels and Grimaldi, 2014).”
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- Authors
- Lefebvre, P.
- Venue
- Journal of Clinical Investigation
- Published
- 2006-03-01
- Volume
- 116
- Issue
- 3
- Pages
- 571-580
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1386122
- OpenAlex
- W2038654926
- Cited by
- 962
- References
- 8
- Citations by year
- 2026: 38 · 2025: 57 · 2024: 44 · 2023: 45 · 2022: 48 · 2021: 40 · 2020: 44 · 2019: 35 · 2018: 34 · 2017: 42 · 2016: 41 · 2015: 38 · 2014: 67 · 2013: 54 · 2012: 50
- FWCI
- 5.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- PPARα, nuclear receptors, energy metabolism, vascular homeostasis, lipid metabolism, glucose homeostasis, fatty acid oxidation, lipoprotein metabolism, anti-inflammatory activity, antiproliferative activity, cholesterol efflux, macrophages, atherosclerosis, fibrates, PPARα agonist, dyslipidemia, metabolic syndrome, cardiovascular disease, adverse effects
- MeSH terms
- Animals, Blood Circulation, Energy Metabolism, Homeostasis, Humans, Metabolic Diseases, PPAR alpha
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