Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health: A Review of Emerging Biologic Pathways

Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health: A Review of Emerging Biologic Pathways

Dariush Mozaffarian, Jason H.Y. Wu

Selected cardiometabolic benefits of flavonoids and potential underlying molecular mechanisms. In vitro and animal studies support bioactivity of purified flavonoids or flavonoid-rich plant extracts across multiple tissues. Relevant molecular pathways seem to include (1) modulation of gene expression and signaling pathways. Enhancement of AMPK (5′-monophosphate-activated protein kinase) phosphorylation and activation appears to be a common mechanism affected by several types of flavonoids. Modulation of other signaling pathways has also been observed including increased expression of PPAR-γ (peroxisome proliferator-activated receptor-γ) and inhibition of NF-κB (nuclear factor-κB) activation; (2) interaction with gut microbiota. Dietary flavonoids may alter gut-microbial composition because of probiotic-like properties and stimulate growth of specific bacteria (eg, Akkermansia muciniphila) that may confer metabolic benefits. Conversely, metabolism of dietary flavonoids by gut bacteria generates downstream metabolites (eg, phenolic acids) that may possess unique properties and reach higher circulating and tissue concentrations compared with parent flavonoids, thus enhancing biological activity of flavonoids; (3) Direct flavonoid–protein interactions. Growing evidence suggests that flavonoids both stimulate and inhibit protein function, including of ion channels in the vasculature and liver and carbohydrate digestive enzymes (α-amylase and α-glucosidase) in the gastrointestinal tract. Such effects may partly contribute to regulation of vascular tone and glucose metabolism. ERK1/2 indicates extracellular signal-regulated kinases 1 and 2; GLUT4, glucose transporter type 4; IRS2, insulin receptor substrate-2; MAPK, mitogen-activated protein kinase; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator-1α; PKA; protein kinase-A; SREBP-1c, sterol regulatory element–binding protein-1c; TG, triglycerides; and TLR4, toll-like receptor 4. (Illustration Credit: Ben Smith.) [Powerpoint File]

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