TY - JOUR
T1 - Red Raspberry Polyphenols Attenuate High-Fat Diet–Driven Activation of NLRP3 Inflammasome and its Paracrine Suppression of Adipogenesis via Histone Modifications
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
N1 - Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/8/1
Y1 - 2020/8/1
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.
KW - adipogenesis
KW - histone modification
KW - nod-like receptor protein 3 inflammasome
KW - polyphenols
KW - red raspberry
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U2 - 10.1002/mnfr.201900995
DO - 10.1002/mnfr.201900995
M3 - Article
C2 - 31786828
AN - SCOPUS:85076363229
SN - 1613-4125
VL - 64
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 15
M1 - 1900995
ER -