Lanthionine synthetase C-like protein 2 (LanCL2) is important for adipogenic differentiation

Debapriya Dutta, Kuan Yu Lai, Adriana Reyes-Ordoñez, Jie Chen, Wilfred Adrianus van der Donk

Research output: Contribution to journalArticle

Abstract

Adipogenic differentiation is a highly regulated process that is necessary for metabolic homeostasis and nutrient sensing. The expression of PPARγ and the subsequent activation of adipogenic genes is critical for the process. In this study, we identified lanthionine synthetase C-like protein 2 (LanCL2) as a positive regulator of adipogenesis in 3T3-L1 cells. Knockdown of LanCL2, but not LanCL1, inhibited adipogenic differentiation, and this effect was not mediated through cAMP or Akt signaling pathways. The expression of early adipogenic markers CCAAT enhancer binding protein β (C/EBPβ) and C/EBPδ remained intact in LanCL2 knockdown cells, but levels of late adipogenic markers PPARγ and C/EBPα were suppressed. The addition of the naturally occurring PPARγ activator 15-deoxy-Δ 12,14 -prostaglandin J2 or conditioned medium from differentiating cells did not restore differentiation, implying that LanCL2 may not be involved in the production of a secreted endogenous PPARγ ligand. Pulldown assays demonstrated a direct physical interaction between LanCL2 and PPARγ. Consistent with a regulatory role of LanCL2, luciferase reporter assays revealed that full transcriptional activation by PPARγ was dependent on LanCL2. Taken together, our study reveals a novel role of LanCL2 in adipogenesis, specifically involved in PPARγ-mediated transactivation of downstream adipogenic genes.

Original languageEnglish (US)
Pages (from-to)1433-1445
Number of pages13
JournalJournal of Lipid Research
Volume59
Issue number8
DOIs
StatePublished - Jan 1 2018

Fingerprint

Peroxisome Proliferator-Activated Receptors
Ligases
Protein C
CCAAT-Enhancer-Binding Proteins
Proteins
Transcriptional Activation
Adipogenesis
Assays
Genes
Chemical activation
3T3-L1 Cells
lanthionine
Conditioned Culture Medium
Luciferases
Nutrients
Homeostasis
Ligands
Food

Keywords

  • 3T3-L1
  • Adipocytes
  • Peroxisome proliferator activated receptor γ

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Lanthionine synthetase C-like protein 2 (LanCL2) is important for adipogenic differentiation. / Dutta, Debapriya; Lai, Kuan Yu; Reyes-Ordoñez, Adriana; Chen, Jie; van der Donk, Wilfred Adrianus.

In: Journal of Lipid Research, Vol. 59, No. 8, 01.01.2018, p. 1433-1445.

Research output: Contribution to journalArticle

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