PPAR agonists, - could tissue targeting pave the way
Abstract
Over the last couple of decades, the PPAR family of transcription factors has received much attention from the pharmaceutical industry due to their profound ability to improve glucose and lipid metabolism upon agonist activation. However, more recently the interest in these nuclear receptors has faded because several clinical trials have shown that it is difficult to develop a ligand that significantly ameliorates glucose and lipid metabolism disorders without concomitantly inducing unacceptable side-effects. Nevertheless, the data also suggests that tissue specific targeting could pave the way to renewed interest and clinical use of PPAR ligands. In this review we summarize the results and learnings from the clinical trials on PPAR agonism and discuss the possibilities for tissue targeting of PPAR ligands by using state of the art technology to fuse them to peptides homing selectively to tissues expressing the cognate surface receptor.
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PPARs are lipid sensors that transcriptionally modulate metabolic programs in response to nutrition and are interesting drug targets to improve metabolic flexibility.
“PPARs are lipid sensors that transcriptionally modulate metabolic programs in response to nutrition and are interesting drug targets to improve metabolic flexibility [reviewed in Bugge and Holst (269)].”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [269]
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- Authors
- Bugge, A., & Holst, D.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Holst, Dorte
- Venue
- Biochimie
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 136
- Pages
- 100-104
- ISSN
- 0037-9042 (ISSN-L)
- 0300-9084
- OpenAlex
- W2557826754
- Cited by
- 14
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 1
- FWCI
- 0.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimie (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 › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- PPAR agonists, peroxisome proliferator-activated receptors, tissue targeting, peptide ligands, nuclear receptors, glucose metabolism, lipid metabolism, adverse effects, clinical trials, drug development
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Thiazolidinediones, Peroxisome Proliferator-Activated Receptors
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