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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-? (TNF-?), and interleukin-6 (IL-6) in RAW264.7 macrophages. Although each compound inhibited the mRNA expression of iNOS (inducible NO synthase), TNF-?, and IL-6, PIC potently inhibited them, and 30 ?mol/L PIC suppressed the LPS- and 3T3-L1-CM-induced mRNA expression of iNOS (70.4% and 69.2% suppression, respectively), TNF-? (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-?; 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.

SUBMITTER: Yamamoto T

PROVIDER: S-EPMC5217925 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Piceatannol exhibits anti-inflammatory effects on macrophages interacting with adipocytes.

Yamamoto Takayuki T Li Yongjia Y Hanafusa Yuki Y Yeh Yu-Sheng YS Maruki-Uchida Hiroko H Kawakami Shinpei S Sai Masahiko M Goto Tsuyoshi T Ito Tatsuhiko T Kawada Teruo T

Food science & nutrition 20160516 1

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), ...[more]

PMID: 28070318

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Project description:Objectives: Pinolenic acid (PNLA), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects. We aimed to investigate the direct anti-inflammatory effect and anti-atherogenic effects of PNLA on activated purified CD14 monocytes from peripheral blood of patients with rheumatoid arthritis (RA) in vitro. Methods: Flow cytometry was used to assess the proportions of CD14 monocytes expressing TNF-α, IL-6, IL-1β, and IL-8 in purified monocytes from patients with RA after lipopolysaccharide (LPS) stimulation with/without PNLA pre-treatment. The whole genomic transcriptome (WGT) profile of PNLA-treated, and LPS-activated monocytes from patients with active RA was investigated by RNA-sequencing. Results: PNLA reduced percentage of monocytes expressing cytokines: TNF-a by 23% (p=0.048), IL-6 by 25% (p=0.011), IL-1B by 23% (p=0.050), IL-8 by 20% (p=0.066). Pathway analysis identified upstream activation of peroxisomes proliferator-activated receptors (PPARs), sirtuin3, and let7miRNA, KLF15 which are anti-inflammatory and antioxidative. In contrast, DAP3, LIF and STAT3, which are involved in TNF-a, and IL-6 signal transduction, were inhibited. Canonical Pathway analysis showed that PNLA inhibited oxidative phosphorylation (p=9.14E-09) and mitochondrial dysfunction (p=4.18E-08), while the sirtuin (SIRTs) signalling pathway was activated (p=8.89E-06) which interfere with the pathophysiologic process of atherosclerosis. Many miRNAs were modulated by PNLA suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously. Multiple miRNAs target pyruvate dehydrogenase kinase-4 (PDK4), single-immunoglobulin interleukin-1 receptor molecule (SIGIRR), mitochondrially encoded ATP synthase membrane subunit 6 (MT-ATP6) and Acetyl-CoA Acyltranferase2 (ACAA2); genes implicated in regulation of lipid and cell metabolism, inflammation, and mitochondrial dysfunction. Conclusion: PNLA has potential anti-atherogenic and immune-metabolic effects on monocytes that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation regulates key miRNAs that are involved in metabolic, mitochondrial, and inflammatory pathways.

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Piceatannol exhibits anti-inflammatory effects on macrophages interacting with adipocytes.

Publications

Piceatannol exhibits anti-inflammatory effects on macrophages interacting with adipocytes.

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