Red Raspberry Polyphenols Attenuate High-Fat Diet–Driven Activation of NLRP3 Inflammasome and its Paracrine Suppression of Adipogenesis via Histone Modifications

Rong Fan, Mikyoung You, Ashley M. Toney, Judy Kim, David Giraud, Yibo Xian, Feng Ye, Liwei Gu, Amanda E. Ramer-Tait, Soonkyu Chung

Research output: Contribution to journalArticle

Abstract

Scope: The authors aim to investigate the mechanisms by which red raspberry (RR) polyphenolic fractions regulate obesity and inflammation with an emphasis on the crosstalk between adipose tissue macrophages (ATM) and adipocyte progenitors. Methods and Results: C57BL/6 male mice are fed either a high-fat (HF) diet or an HF diet supplemented with a RR polyphenolic fraction from whole fruit, pulp, or seed. Supplementation with pulp significantly increases energy expenditure and reduces HF-diet-induced obesity and insulin resistance. The pulp, and to a lesser extent, whole polyphenols, decreases the recruitment of ATM, activation of the nod-like receptor protein 3 (NLRP3) inflammasome, and adipocyte hypertrophy, which is associated with epigenetic modulation of adipogenesis (e.g., H3K27Ac, H3K9Ac). Results from an IL-1β reporter assay in J774 macrophages recapitulate the inhibitory role of RR polyphenols on NLRP3 inflammasome activation. Using conditioned media from macrophages, it is demonstrated that RR polyphenols reverse the IL-1β-mediated epigenetic suppression of H3K27Ac in adipocyte progenitor cells. Conclusions: RR polyphenols from pulp and whole fruit serve as an inhibitor for NLRP3 inflammasome activation and an epigenetic modifier to regulate adipogenesis, which confers resistance against diet-induced obesity and metabolic dysfunction.

Original languageEnglish (US)
Article number1900995
JournalMolecular Nutrition and Food Research
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Histone Code
Inflammasomes
Rubus idaeus
Adipogenesis
Polyphenols
histones
polyphenols
Fats
High Fat Diet
receptors
Adipocytes
Epigenomics
high fat diet
lipids
adipocytes
epigenetics
Obesity
Macrophages
pulp
Proteins

Keywords

  • adipogenesis
  • histone modification
  • nod-like receptor protein 3 inflammasome
  • polyphenols
  • red raspberry

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

Cite this

Red Raspberry Polyphenols Attenuate High-Fat Diet–Driven Activation of NLRP3 Inflammasome and its Paracrine Suppression of Adipogenesis via Histone Modifications. / Fan, Rong; You, Mikyoung; Toney, Ashley M.; Kim, Judy; Giraud, David; Xian, Yibo; Ye, Feng; Gu, Liwei; Ramer-Tait, Amanda E.; Chung, Soonkyu.

In: Molecular Nutrition and Food Research, 01.01.2019.

Research output: Contribution to journalArticle

Fan, Rong ; You, Mikyoung ; Toney, Ashley M. ; Kim, Judy ; Giraud, David ; Xian, Yibo ; Ye, Feng ; Gu, Liwei ; Ramer-Tait, Amanda E. ; Chung, Soonkyu. / Red Raspberry Polyphenols Attenuate High-Fat Diet–Driven Activation of NLRP3 Inflammasome and its Paracrine Suppression of Adipogenesis via Histone Modifications. In: Molecular Nutrition and Food Research. 2019.
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abstract = "Scope: The authors aim to investigate the mechanisms by which red raspberry (RR) polyphenolic fractions regulate obesity and inflammation with an emphasis on the crosstalk between adipose tissue macrophages (ATM) and adipocyte progenitors. Methods and Results: C57BL/6 male mice are fed either a high-fat (HF) diet or an HF diet supplemented with a RR polyphenolic fraction from whole fruit, pulp, or seed. Supplementation with pulp significantly increases energy expenditure and reduces HF-diet-induced obesity and insulin resistance. The pulp, and to a lesser extent, whole polyphenols, decreases the recruitment of ATM, activation of the nod-like receptor protein 3 (NLRP3) inflammasome, and adipocyte hypertrophy, which is associated with epigenetic modulation of adipogenesis (e.g., H3K27Ac, H3K9Ac). Results from an IL-1β reporter assay in J774 macrophages recapitulate the inhibitory role of RR polyphenols on NLRP3 inflammasome activation. Using conditioned media from macrophages, it is demonstrated that RR polyphenols reverse the IL-1β-mediated epigenetic suppression of H3K27Ac in adipocyte progenitor cells. Conclusions: RR polyphenols from pulp and whole fruit serve as an inhibitor for NLRP3 inflammasome activation and an epigenetic modifier to regulate adipogenesis, which confers resistance against diet-induced obesity and metabolic dysfunction.",
keywords = "adipogenesis, histone modification, nod-like receptor protein 3 inflammasome, polyphenols, red raspberry",
author = "Rong Fan and Mikyoung You and Toney, {Ashley M.} and Judy Kim and David Giraud and Yibo Xian and Feng Ye and Liwei Gu and Ramer-Tait, {Amanda E.} and Soonkyu Chung",
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AU - Fan, Rong

AU - You, Mikyoung

AU - Toney, Ashley M.

AU - Kim, Judy

AU - Giraud, David

AU - Xian, Yibo

AU - Ye, Feng

AU - Gu, Liwei

AU - Ramer-Tait, Amanda E.

AU - Chung, Soonkyu

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N2 - Scope: The authors aim to investigate the mechanisms by which red raspberry (RR) polyphenolic fractions regulate obesity and inflammation with an emphasis on the crosstalk between adipose tissue macrophages (ATM) and adipocyte progenitors. Methods and Results: C57BL/6 male mice are fed either a high-fat (HF) diet or an HF diet supplemented with a RR polyphenolic fraction from whole fruit, pulp, or seed. Supplementation with pulp significantly increases energy expenditure and reduces HF-diet-induced obesity and insulin resistance. The pulp, and to a lesser extent, whole polyphenols, decreases the recruitment of ATM, activation of the nod-like receptor protein 3 (NLRP3) inflammasome, and adipocyte hypertrophy, which is associated with epigenetic modulation of adipogenesis (e.g., H3K27Ac, H3K9Ac). Results from an IL-1β reporter assay in J774 macrophages recapitulate the inhibitory role of RR polyphenols on NLRP3 inflammasome activation. Using conditioned media from macrophages, it is demonstrated that RR polyphenols reverse the IL-1β-mediated epigenetic suppression of H3K27Ac in adipocyte progenitor cells. Conclusions: RR polyphenols from pulp and whole fruit serve as an inhibitor for NLRP3 inflammasome activation and an epigenetic modifier to regulate adipogenesis, which confers resistance against diet-induced obesity and metabolic dysfunction.

AB - Scope: The authors aim to investigate the mechanisms by which red raspberry (RR) polyphenolic fractions regulate obesity and inflammation with an emphasis on the crosstalk between adipose tissue macrophages (ATM) and adipocyte progenitors. Methods and Results: C57BL/6 male mice are fed either a high-fat (HF) diet or an HF diet supplemented with a RR polyphenolic fraction from whole fruit, pulp, or seed. Supplementation with pulp significantly increases energy expenditure and reduces HF-diet-induced obesity and insulin resistance. The pulp, and to a lesser extent, whole polyphenols, decreases the recruitment of ATM, activation of the nod-like receptor protein 3 (NLRP3) inflammasome, and adipocyte hypertrophy, which is associated with epigenetic modulation of adipogenesis (e.g., H3K27Ac, H3K9Ac). Results from an IL-1β reporter assay in J774 macrophages recapitulate the inhibitory role of RR polyphenols on NLRP3 inflammasome activation. Using conditioned media from macrophages, it is demonstrated that RR polyphenols reverse the IL-1β-mediated epigenetic suppression of H3K27Ac in adipocyte progenitor cells. Conclusions: RR polyphenols from pulp and whole fruit serve as an inhibitor for NLRP3 inflammasome activation and an epigenetic modifier to regulate adipogenesis, which confers resistance against diet-induced obesity and metabolic dysfunction.

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KW - polyphenols

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