title: Modulation of cAMP levels by high-fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression.
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. © 2016 BioFactors, 43(1):42-53, 2017.
authors.affiliation: Vascular Biology Laboratory, JM USDA-Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Zingg
authors.affiliation: Vascular Biology Laboratory, JM USDA-Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA.
authors.forename: Syeda T
authors.initials: ST
authors.lastname: Hasan
authors.affiliation: Vascular Biology Laboratory, JM USDA-Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Experimental Medicine, Section of General Pathology, University of Genoa, Genoa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Canepa
authors.affiliation: Department of Experimental Medicine, Section of General Pathology, University of Genoa, Genoa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciarelli
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Villacorta
authors.affiliation: Vascular Biology Laboratory, JM USDA-Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA.
authors.forename: Angelo
authors.initials: A
authors.lastname: Azzi
authors.affiliation: Vascular Biology Laboratory, JM USDA-Human Nutrition Research Center on Aging, Tufts University, Boston, MA, 02111, USA.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Meydani
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D059305:Diet, High-Fat; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational
chemical_list: D018955:CD36 Antigens; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D000960:Hypolipidemic Agents; D000242:Cyclic AMP; D003474:Curcumin
keywords: CD36; CREB; NRF2; PPARγ; atherosclerosis; cAMP signaling; curcumin; fat accumulation; fat metabolism; gene expression; inflammation; obesity