Cited by 489Peroxisome Proliferator-Activated ReceptorsCircadian rhythm and melatoninAdipose Tissue and Metabolism

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PER2 Controls Lipid Metabolism by Direct Regulation of PPARγ

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Grimaldi, Benedetto, Bellet, Marina Maria, Katada, Sayako, Astarita, Giuseppe, Hirayama, Jun, Amin, Rajesh H., Granneman, James G., Piomelli, Daniele, Leff, Todd, Sassone-Corsi, Paolo·2010·Cell Metabolism

DOI 10.1016/j.cmet.2010.10.005PMC PMC4103168

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Abstract

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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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: Grimaldi, Benedetto
Bellet, Marina Maria
Katada, Sayako
Astarita, Giuseppe
Hirayama, Jun
Amin, Rajesh H.
Granneman, James G.
Piomelli, Daniele
Leff, Todd
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2010-11
Volume: 12
Issue: 5
Pages: 509-520
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2010.10.005
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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PER2 Controls Lipid Metabolism by Direct Regulation of PPARγ

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