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Shared PPARα/γ Target Genes Regulate Brown Adipocyte Thermogenic Function.

Yachen Shen1, Yvonne Su1, Francisco J Silva2

  • 1Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Cell Reports
|March 5, 2020
PubMed
Summary
This summary is machine-generated.

Nuclear receptors PPARα and PPARγ share binding sites in brown adipose tissue (BAT), regulating genes like cathepsin Z (CTSZ). CTSZ is crucial for brown adipocyte thermogenic function and mitochondrial respiration.

Keywords:
CTSZPPARαPPARγbrown adipocytesfenofibraterosiglitazonethermogenesis

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Area of Science:

  • Molecular Endocrinology
  • Adipocyte Biology
  • Metabolic Regulation

Background:

  • Brown adipose tissue (BAT) is vital for thermogenesis and obesity suppression.
  • Nuclear receptors Peroxisome proliferator-activated receptor alpha (PPARα) and PPARγ influence brown adipocyte function, but their interplay in BAT is unclear.

Purpose of the Study:

  • To investigate the interplay between PPARα and PPARγ genomic binding in brown adipose tissue.
  • To identify shared target genes regulated by PPARα and PPARγ in BAT.
  • To determine the role of identified target genes in brown adipocyte thermogenic function.

Main Methods:

  • ChIP-sequencing to map PPARα and PPARγ genomic binding sites in BAT.
  • Integration of genomic occupancy data with cold-responsive BAT transcriptomes.
  • Functional studies using mouse and human brown adipocytes to assess gene function.

Main Results:

  • PPARα and PPARγ share a significant number of genomic binding sites in BAT.
  • Common binding sites are more strongly associated with BAT function than PPARγ-selective sites.
  • Cathepsin Z (CTSZ) was identified as a shared PPARα/γ target gene, essential for mitochondrial respiration in brown adipocytes.

Conclusions:

  • PPARα and PPARγ coordinately regulate gene expression in brown adipose tissue.
  • Cathepsin Z (CTSZ) is a novel, shared PPARα/γ target gene critical for brown adipocyte thermogenic capacity.
  • Targeting CTSZ may offer a therapeutic strategy for metabolic disorders associated with impaired BAT function.