Integrated physiology and systems biology of PPARα.
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TLDR
This review addresses the functional role of PPARα in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPAR α, with a focus on liver.Abstract:
The Peroxisome Proliferator Activated Receptor alpha (PPARα) is a transcription factor that plays a major role in metabolic regulation. This review addresses the functional role of PPARα in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPARα, with a focus on liver. A distinction is made between the impact of PPARα on metabolism upon physiological, pharmacological, and nutritional activation. Low and high throughput gene expression analyses have allowed the creation of a comprehensive map illustrating the role of PPARα as master regulator of lipid metabolism via regulation of numerous genes. The map puts PPARα at the center of a regulatory hub impacting fatty acid uptake, fatty acid activation, intracellular fatty acid binding, mitochondrial and peroxisomal fatty acid oxidation, ketogenesis, triglyceride turnover, lipid droplet biology, gluconeogenesis, and bile synthesis/secretion. In addition, PPARα governs the expression of several secreted proteins that exert local and endocrine functions.read more
Citations
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Journal ArticleDOI
Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD
Alexandra Montagner,Arnaud Polizzi,Edwin Fouché,Simon Ducheix,Yannick Lippi,Frédéric Lasserre,Valentin Barquissau,Valentin Barquissau,Marion Régnier,Céline Lukowicz,Fadila Benhamed,Fadila Benhamed,Fadila Benhamed,Alison Iroz,Alison Iroz,Alison Iroz,Justine Bertrand-Michel,Justine Bertrand-Michel,Talal Al Saati,Patricia Cano,Laila Mselli-Lakhal,Gilles Mithieux,Fabienne Rajas,Sandrine Lagarrigue,Sandrine Lagarrigue,Sandrine Lagarrigue,Thierry Pineau,Nicolas Loiseau,Catherine Postic,Catherine Postic,Catherine Postic,Dominique Langin,Dominique Langin,Dominique Langin,Walter Wahli,Walter Wahli,Walter Wahli,Hervé Guillou +37 more
TL;DR: Hepatocyte PPARα deletion impaired fatty acid catabolism, resulting in hepatic lipid accumulation during fasting and in two preclinical models of steatosis, underscore the potential of hepatocyte PParα as a drug target for NAFLD.
Journal ArticleDOI
Molecular Actions of PPARα in Lipid Metabolism and Inflammation.
Nadia Bougarne,Basiel Weyers,Sofie Desmet,Julie Deckers,David W. Ray,Bart Staels,Karolien De Bosscher +6 more
TL;DR: The full potential of this nuclear receptor subtype as a versatile drug target with high plasticity becomes increasingly clear, and a novel generation of agonists may pave the way for novel fields of applications.
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Mitochondrial biogenesis and dynamics in the developing and diseased heart
TL;DR: The regulatory circuitry and downstream events involved in mitochondrial biogenesis and its coordination with mitochondrial dynamics in developing and diseased hearts are described.
Journal ArticleDOI
An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
Adil Mardinoglu,Hao Wu,Elias Björnson,Cheng Zhang,Antti Hakkarainen,Sari M. Räsänen,Sunjae Lee,Rosellina Margherita Mancina,Mattias Bergentall,Kirsi H. Pietiläinen,Sanni Söderlund,Niina Matikainen,Marcus Ståhlman,Per Olof Bergh,Martin Adiels,Brian D. Piening,Marit Granér,Nina Lundbom,Kevin Jon Williams,Stefano Romeo,Jens Nielsen,Michael Snyder,Mathias Uhlén,Göran Bergström,Rosie Perkins,Hanns-Ulrich Marschall,Fredrik Bäckhed,Marja-Riitta Taskinen,Jan Borén +28 more
TL;DR: A short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and the resulting alterations in metabolism and the gut microbiota are characterized using a multi-omics approach to highlight the potential of exploring diet-microbiota interactions for treatingNAFLD.
Journal ArticleDOI
Rationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study.
Aruna D. Pradhan,Nina P. Paynter,Brendan M. Everett,Robert J. Glynn,Pierre Amarenco,Marshall B. Elam,Henry N. Ginsberg,William R. Hiatt,Shun Ishibashi,Wolfgang Koenig,Børge G. Nordestgaard,Jean Charles Fruchart,Peter Libby,Paul M. Ridker +13 more
TL;DR: The selective peroxisome proliferator‐activated receptor alpha modulator (SPPARM‐&agr;), pemafibrate, will be used to target residual cardiovascular risk remaining after treatment to reduce low‐density lipoprotein cholesterol (LDL‐C) in individuals with the dyslipidemia of type 2 diabetes mellitus (T2).
References
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Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators
Isabelle Issemann,Stephen Green +1 more
TL;DR: A member of the steroid hormone receptor superfamily of ligand-activated transcription factors is cloned that is activated by a diverse class of rodent hepatocarcinogens that causes proliferation of peroxisomes.
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Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors α and δ
TL;DR: It is shown here that specific FAs, eicosanoids, and hypolipidemic drugs are ligands for PPARα or PPARδ, and a novel conformation-based assay is developed that screens activators for their ability to bind to PPAR α/δ and induce DNA binding.
Journal ArticleDOI
Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ
Steven A. Kliewer,Scott S. Sundseth,Stacey A. Jones,Peter Brown,G. Bruce Wisely,Cecilia S. Koble,Pallavi R. Devchand,Walter Wahli,Timothy M. Willson,James M. Lenhard,Jürgen M. Lehmann +10 more
TL;DR: Evidence that PPARs serve as physiological sensors of lipid levels is provided and a molecular mechanism whereby dietary fatty acids can modulate lipid homeostasis is suggested.
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Nuclear receptors and lipid physiology: opening the X-files.
TL;DR: Some general principles that govern the actions of this class of bioactive lipids and their nuclear receptors are considered here, and the scheme that emerges reveals a complex molecular script at work.
Journal ArticleDOI
Roles of PPARs in health and disease.
TL;DR: The latest developments in the PPAR field are presented, with particular emphasis on the physiological function ofPPARs during various nutritional states, and the possible role of PPARs in several chronic diseases.
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