Modulation of cAMP levels by high-fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression

Jean Marc Zingg, Syeda T. Hasan, Kiyotaka Nakagawa, Elisa Canepa, Roberta Ricciarelli, Luis Villacorta, Angelo Azzi, Mohsen Meydani

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlr−/− mice fed a high-fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of fatty acid transport proteins (CD36/FAT, FABP4/aP2) in peritoneal macrophages. In this study, we analyzed the molecular mechanisms by which curcumin (500, 1000, 1500 mg/kg diet, for 4 months) may influence plasma and tissue lipid levels in Ldlr−/− mice fed an HFD. In liver, HFD significantly suppressed cAMP levels, and curcumin restored almost normal levels. Similar trends were observed in adipose tissues, but not in brain, skeletal muscle, spleen, and kidney. Treatment with curcumin increased phosphorylation of CREB in liver, what may play a role in regulatory effects of curcumin in lipid homeostasis. In cell lines, curcumin increased the level of cAMP, activated the transcription factor CREB and the human CD36 promoter via a sequence containing a consensus CREB response element. Regulatory effects of HFD and Cur on gene expression were observed in liver, less in skeletal muscle and not in brain. Since the cAMP/protein kinase A (PKA)/CREB pathway plays an important role in lipid homeostasis, energy expenditure, and thermogenesis by increasing lipolysis and fatty acid β-oxidation, an increase in cAMP levels induced by curcumin may contribute to its hypolipidemic and anti-atherosclerotic effects.

Original languageEnglish
Pages (from-to)42-53
Number of pages12
JournalBioFactors
Volume43
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1
Externally publishedYes

Keywords

  • CD36
  • CREB
  • NRF2
  • PPARγ
  • atherosclerosis
  • cAMP signaling
  • curcumin
  • fat accumulation
  • fat metabolism
  • gene expression
  • inflammation
  • obesity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Clinical Biochemistry

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