Shinpei Kawakami

Piceatannol and its metabolite, isorhapontigenin, induce SIRT1 expression in THP-1 human monocytic cell line.

Piceatannol is a phytochemical that is present in large amounts in passion fruit (Passiflora edulis) seeds, and is an analog of resveratrol. Recently, the absorption and metabolism of piceatannol were investigated in rats, and isorhapontigenin, O-methyl piceatannol, was detected as a piceatannol metabolite in rat plasma. To elucidate the function of piceatannol and its metabolites, we investigated the expression of sirtuin 1 (SIRT1) in THP-1 monocytic cells after treatment with piceatannol and its metabolites, and compared their effects with those of resveratrol and its metabolites. Piceatannol and resveratrol upregulated the expression levels of SIRT1 mRNA and SIRT1 protein. An extract of passion fruit seeds, which contained high levels of piceatannol, also upregulated SIRT1 mRNA expression. As for the metabolites, isorhapontigenin upregulated SIRT1 mRNA expression, whereas resveratrol glucuronides and sulfate did not affect SIRT1 expression. These findings indicate that after intake of piceatannol, not only piceatannol itself, but also its metabolite, isorhapontigenin, contributed to the upregulation of SIRT1 expression.

Piceatannol exhibits anti-inflammatory effects on macrophages interacting with adipocytes

Abstract Piceatannol (PIC), a natural analog of resveratrol (RES), is a phytochemical found in passion fruit seeds. To clarify the effects of PIC on obesity‐induced inflammation in adipose tissue, we investigated the anti‐inflammatory activity of PIC‐related compounds (PIC, RES, and metabolites from PIC) in culture models of obese adipose tissue. Lipopolysaccharide (LPS) and conditioned medium from 3T3‐L1 adipocytes (3T3‐L1‐CM) enhanced proinflammatory gene expression and synthesis of nitric oxide (NO), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) in RAW264.7 macrophages. Although each compound inhibited the mRNA expression of iNOS (inducible NO synthase), TNF‐α, and IL‐6, PIC potently inhibited them, and 30 μmol/L PIC suppressed the LPS‐ and 3T3‐L1‐CM‐induced mRNA expression of iNOS (70.4% and 69.2% suppression, respectively), TNF‐α (42.6% and 47.0% suppression), and IL‐6 (27.3% and 42.1% suppression). PIC also significantly suppressed production of NO (80.3% suppression) and inflammatory cytokines (TNF‐α; 33.7% suppression, IL‐6; 66.5% suppression). Furthermore, PIC was found to rescue the uncoupling protein 1 mRNA expression induced by isoproterenol in 10T1/2 adipocytes, which was suppressed by LPS‐activated macrophages. These results suggest that PIC may attenuate the pathologic inflammation triggered by adipose tissues.

ACCUMULATION OF SNAP25 IN MOUSE GUSTATORY AND SOMATOSENSORY CORTICES IN RESPONSE TO FOOD AND CHEMICAL STIMULATION

Food intake stimuli, including taste, somatosensory, and tactile stimuli, are received by receptors in the oral cavity, and this information is then transferred to the cerebral cortex. Signals from recently ingested food during the weaning period can affect synaptic transmission, resulting in biochemical changes in the cerebral cortex that modify gustatory and somatosensory nervous system plasticity. In this study, we investigated the expression patterns of molecular markers in mouse gustatory and somatosensory cortices during the weaning period. The expression of synaptosomal-associated protein 25 (SNAP25), a component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, was increased in the insular and somatosensory cortices at postnatal week 3 compared to postnatal week 2. Additionally, SNAP25 protein in the cerebral cortex accumulated in weaning mice fed solid food but not in mice fed only mothers milk at the weaning stage. Chemical stimulation by saccharin or capsaicin at the weaning stage also increased SNAP25 immunoreactivity in the insular or somatosensory cortical area, respectively. These results suggest that recently ingested chemical signals in the oral cavity during weaning increase the accumulation of SNAP25 in the gustatory and somatosensory cortices and promote neural plasticity during the development of the gustatory and somatosensory nervous systems.

Differential expression analysis throughout the weaning period in the mouse cerebral cortex.

At weaning, mammals switch from drinking mothers milk to eating foods of environmental origin. These foods contain natural compounds with novel tastes and textures, which are provided to the young for the first time following the termination of breastfeeding. This novel eating experience may alter the cognitive brain function of mammalian babies, increasing their reactions to their food environments. Because the cerebral cortex is a central organ for cognition and learning, we investigated differences in whole-gene expression profiles in the mouse cerebral cortex using microarray analysis before and after weaning. Of 45,037 murine genes, 35 genes were upregulated and 31 genes were downregulated, in response to weaning. In particular, immediate early genes, molecular chaperones, and myelin-related genes were upregulated. In situ hybridization analysis revealed that the mRNA for an immediate early gene, Egr-2/KROX-20, was transported from the nucleus to the cell body at layer 5/6 of the somatosensory cortex during weaning. In contrast, in animals without any food supply other than mothers milk, Egr-2/KROX-20 mRNA was retained within the nucleus at the somatosensory cortex. These data suggest that the novel experience of food intake modulates gene expression profiles in the murine cerebral cortex at the weaning stage.