Studies on the bio-regulatory function of polyphenols from the viewpoints of themultiple-organs crosstalk and circadian rhythm.
Yoko Yamashita (Kobe University, Department of Agribioscience)yoko.y@crystal.kobe-u.ac.jp
Abstract
Recently, much attention has been paid to the prevention of lifestyle-related diseases by food factors.
Polyphenols are potent candidates for effective food factors to promote the human health. Among
polyphenols, the author focused on flavan-3-ols, in particular procyanidins, which are contained in various
plant foods, such as cacao and black soybean. Although bioavailability of procyanidins with a higher degreeof polymerization are poor, many evidences have been accumulated to date on the health beneficial functionsof procyanidins. For example, procyanidins-rich extracts or foods possess prevention of hyperglycemia,
insulin resistance and obesity, and improvement of vascular function. However, there are few data addressing
the primary target molecule of procyanidins for metabolic regulation and maintenance of homeostasis in ourbody. Therefore, the author hypothesized procyanidins firstly affect the digestive tract and build a multipleorgans network. It was found that procyanidins promoted secretion of an intestinal hormone (one of theincretin hormones), glucagon like peptide-1 (GLP-1) from L cells, the enteroendocrine cells. GLP-1 regulates
various functions, including promotion of insulin secretion from pancreatic β cells. It is known that certain
nutrients such as glucose and glutamate secrete GLP-1, but it is unclear whether non-nutrients secrete thishormone. Recently, the author found that a single oral ingestion of procyanidins prevented postprandial
hyperglycemia accompanied by increasing insulin secretion through promoting GLP-1 secretion in mice. As
underling molecular mechanism of anti-hyperglycemia, increased insulin by procyanidins promoted
translocation of glucose transporter 4 in skeletal muscle. Interestingly, this health beneficial function ofprocyanidins was dependent on the degree of polymerization, and cinnamtannin A2, one of the tetramer
procyanidins, showed the strongest effects. These results indicated that cinnamtannin A2 revealed an insulinmimetic action in vivo, but this action was not observed in vitro cell culture study. The author also found thatprocyanidin-suppressed hyperglycemia had a suitable administration timing in mice, because GLP-1
secretion was regulated by clock gene. Procyanidin also prevented overeating through suppressing theexpression of food intake factors in the brain of obese model mice, but not normal mice. This function wasalso regulated by increased GLP-1 secretion. Moreover, the intake of procyanidins contributed to theimprovement of vascular function by promoting nitric oxide (NO) production. As for a putative underlying
mechanism, GLP-1 secreted by procyanidins and increased the phosphorylation of endothelial nitric oxide
synthase (eNOS) in vascular endothelial cells. In conclusion, these results indicate that procyanidins havevarious health beneficial functions through GLP-1 secretion from the digestive tract. Thus, bio-regulatory
functions of procyanidins are regulated through the crosstalk among multiple-organs and circadian rhythm.