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PER2 Controls Lipid Metabolism by Direct Regulation of PPARγ
Open accessAbstract
Accumulating evidence highlights intriguing interplays between circadian and metabolic pathways. We show that PER2 directly and specifically represses PPARγ, a nuclear receptor critical in adipogenesis, insulin sensitivity, and inflammatory response. PER2-deficient mice display altered lipid metabolism with drastic reduction of total triacylglycerol and nonesterified fatty acids. PER2 exerts its inhibitory function by blocking PPARγ recruitment to target promoters and thereby transcriptional activation. Whole-genome microarray profiling demonstrates that PER2 dictates the specificity of PPARγ transcriptional activity. Indeed, lack of PER2 results in enhanced adipocyte differentiation of cultured fibroblasts. PER2 targets S112 in PPARγ, a residue whose mutation has been associated with altered lipid metabolism. Lipidomic profiling demonstrates that PER2 is necessary for normal lipid metabolism in white adipocyte tissue. Our findings support a scenario in which PER2 controls the proadipogenic activity of PPARγ by operating as its natural modulator, thereby revealing potential avenues of pharmacological and therapeutic intervention.
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“PER2 controls lipid metabolism by directly repressing PPARG's proadipogenic activity (Grimaldi et al. 2010).”
From Archaic Introgression Shaped Human Circadian Traits (2023) · cites this paper as Grimaldi et al. 2010
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“as well as a reduction in fat pad mass and plasma lipid levels [23].”
From Circadian control of glucose metabolism (2014) · cites this paper as [23]
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Metadata
- Authors
- Grimaldi, B., Bellet, M. M., Katada, S., Astarita, G., Hirayama, J., Amin, R. H., Granneman, J. G., Piomelli, D., Leff, T., & Sassone-Corsi, P.
- Affiliations
- University of California, Irvine (US)
- Wayne State University (US)
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 12
- Issue
- 5
- Pages
- 509-520
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4103168
- OpenAlex
- W2089749987
- Cited by
- 489
- References
- 52
- Citations by year
- 2026: 19 · 2025: 35 · 2024: 35 · 2023: 37 · 2022: 39 · 2021: 38 · 2020: 39 · 2019: 34 · 2018: 25 · 2017: 29 · 2016: 24 · 2015: 31 · 2014: 34 · 2013: 33 · 2012: 20
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 989 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health (R01-GM081634-01, R21 AG033888)
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- Per2, PPARγ, circadian clock, lipid metabolism, adipogenesis, transcriptional repression, white adipose tissue, triglycerides, free fatty acids, nuclear receptor regulation
- MeSH terms
- Animals, Transcriptional Activation, Gene Expression, Gene Deletion, Adipocytes, NIH 3T3 Cells, 3T3-L1 Cells, PPAR gamma, Adipogenesis, Lipid Metabolism, Mice, Protein Interaction Domains and Motifs, Period Circadian Proteins
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