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.

Identification of Differentially Expressed Micrornas Associate with Glucose Metabolism in Different Organs of Blunt Snout Bream (Megalobrama amblycephala)

“…Using Illumina sequencing and bioinformatics analysis, we identified 79, 124 and 77 DEMs (including 53, 79 and 34 conserved known miRNAs, respectively) that responded in total to HSD treatment in intestines, livers, and brains of M. amblycephala , respectively. GO classification and KEGG pathway analysis for predicted targets of the DEMs showed that these DEMs were associated with the PPAR pathway [11,12,13], the cAMP response element-binding protein [14], and the insulin signaling pathway [12,13,15], which are associated with metabolism regulation of glucose and lipid metabolic pathways and biosynthetic processes, demonstrating the important roles of these DEMs in glucose and lipid metabolisms.…”

“…Research showed that the appropriate carbohydrate ratio in the feed of M. amblycephala is 30–34%, and higher carbohydrate feeding results in glucose intolerance responses including declined glucose metabolic enzyme activity and liver antioxidant abilities, persistent hyperglycemia, and even increased susceptibility to pathogenic bacteria [8,9,10]. For molecular illumination, excessive glucose load in M. amblycephala caused a consequence of metabolic disorders and dysfunctions in biological processes and molecular pathways in glucose and lipid metabolisms, including the peroxisome proliferator-activated receptor (PPAR) pathway [11,12,13], the cyclic adenosine monophosphate(cAMP) response element-binding protein [14], and the insulin signaling pathway [12,13,15], which associate with metabolism regulation. In addition, this dysregulation could be regulated by abnormal expression of genes and microRNAs (miRNAs, single-stranded non-coding RNA molecules length at 18–25 nucleotides) in response to those stimuli.…”

Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia

“…CD36, a fatty acid transport protein, inhibits myocardial PKA activity and cAMP levels through tyrosine kinase-dependent mechanisms such as JNK or p38373839. CD36 is recently reported as an MMP-9 substrate27.…”

Vitamin E: Regulatory Role on Signal Transduction

“…Accordingly, 4‐hydroxynonenal is increased with vitamin E deficiency and macrophage foam cells derived 4‐hydroxynonenal induces senescence in endothelial cells . As with oxLDL and a few specific lipids , CD36 is up‐regulated by 4‐hydroxynonenal involving the NRF2 transcription factor binding sites present in the CD36 promoter of mouse and humans possibly triggering senescence .…”

“…Accordingly, 4-hydroxynonenal is increased with vitamin E deficiency (272) and macrophage foam cells derived 4hydroxynonenal induces senescence in endothelial cells (273). As with oxLDL and a few specific lipids (161,274), CD36 is upregulated by 4-hydroxynonenal involving the NRF2 transcription factor binding sites present in the CD36 promoter of mouse and humans possibly triggering senescence (156,275). Delaying cellular senescence in vivo by clearance of senescent cells by drugs or reducing their senescent phenotype by long-term supplementation with bioactive molecules such as vitamin E may play a role in the prevention of disease by having a positive effect on general health and health span, but an effect on lifespan remains controversial (265,268,276,277).…”