Black tea polyphenols mimic insulin/insulin-like growth factor-1 signalling to the longevity factor FOXO1a.
In vertebrates and invertebrates, relationships between diet and health are controlled by a conserved signalling pathway responsive to insulin-like ligands. In invertebrate models for example, forkhead transcription factor family O (FOXO) transcription factors in this pathway regulate the rate of aging in response to dietary cues, and in vertebrates, obesity and age-induced deficits in the same pathway are thought to contribute to dysregulation of hepatic gluconeogenesis through genes such as phosphoenolpyruvate carboxykinase (PEPCK). Recently, we have begun to screen for dietary constituents capable of regulating this pathway in our cell culture model. Here, we identify three black tea theaflavins, theaflavin 3-O-gallate, theaflavin 3'-O-gallate, theaflavin 3,3'di-O-gallate and thearubigins as novel mimics of insulin/IGF-1 action on mammalian FOXO1a, PEPCK and moreover we provide evidence that the effects on this pathway of the green tea constituent (-)-epigallocatechin gallate depend on its ability to be converted into these larger structures. With the exception of water, tea is the most popular drink globally, but despite this, little is known about the biological availability of black tea polyphenols in vivo or the molecular target(s) mediating the effects presented here. Further investigation in these two areas might provide insight into how age-related metabolic disease may be deferred.
Cameron
Amy R
AR
Neurosciences Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
Anton
Siobhan
S
Melville
Laura
L
Houston
Nicola P
NP
Dayal
Saurabh
S
McDougall
Gordon J
GJ
Stewart
Derek
D
Rena
Graham
G
D000818:Animals; D044946:Biflavonoids / Q000032:analysis / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008136:Longevity; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013662:Tea / Q000737:chemistry*
D044946:Biflavonoids; C085126:FOXO1 protein, human; D005419:Flavonoids; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D007328:Insulin; D010636:Phenols; D059808:Polyphenols; D013662:Tea; C056068:theaflavin; D007334:Insulin-Like Growth Factor I; D002392:Catechin; C045651:epigallocatechin gallate; C069767:phosphoenolpyruvate carboxylase kinase; D017346:Protein Serine-Threonine Kinases