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Published on: May 4, 2021
Red Raspberry Polyphenols Attenuate High-Fat Diet-Driven Activation of NLRP3 Inflammasome and its Paracrine
Rong Fan1, Mikyoung You1, Ashley M Toney1
1Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE, 68583, USA.
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.
Insights
Red raspberry polyphenols reduce obesity and inflammation by inhibiting NLRP3 inflammasome activation and modulating epigenetics in adipocytes. This study highlights their potential for metabolic health.
Area of Science:
- Nutrition Science
- Molecular Biology
- Immunology
Background:
- Obesity and metabolic dysfunction are linked to chronic inflammation.
- Adipose tissue macrophages (ATM) and adipocyte progenitors play key roles in metabolic health.
- Polyphenols from fruits like red raspberry (RR) show potential health benefits.
Purpose of the Study:
- To investigate how RR polyphenolic fractions regulate obesity and inflammation.
- To elucidate the mechanisms involving crosstalk between ATM and adipocyte progenitors.
- To explore the epigenetic modifications influenced by RR polyphenols.
Main Methods:
- Feeding C57BL/6 male mice high-fat (HF) diets with or without RR polyphenolic fractions (whole fruit, pulp, seed).
- Assessing energy expenditure, obesity, insulin resistance, ATM recruitment, NLRP3 inflammasome activation, and adipocyte hypertrophy.
- Utilizing IL-1β reporter assays and conditioned media to study epigenetic modulation (H3K27Ac, H3K9Ac) in macrophages and adipocyte progenitors.
Main Results:
- Pulp supplementation significantly increased energy expenditure and reduced obesity and insulin resistance.
- RR polyphenols, particularly from pulp, decreased ATM recruitment, NLRP3 inflammasome activation, and adipocyte hypertrophy.
- Epigenetic modifications, including H3K27Ac and H3K9Ac, were modulated, suggesting a role in regulating adipogenesis.
Conclusions:
- RR polyphenols from pulp and whole fruit inhibit NLRP3 inflammasome activation.
- RR polyphenols act as epigenetic modifiers regulating adipogenesis.
- These actions confer resistance against diet-induced obesity and metabolic dysfunction.
