Secretion of a gastrointestinal hormone, cholecystokinin, by hop-derived bitter components activates sympathetic nerves in brown adipose tissue.

Matured hop bitter acids (MHBA) are oxidation products from bitter components in hops, which are used widely as food materials to add flavor and bitterness in beer production. Our previous study has shown that MHBA induces thermogenesis in brown adipose tissue (BAT) via sympathetic nerves in rodents and reduces body fat in healthy adults. However, it is unclear how MHBA affects the sympathetic nervous system. In this study, we demonstrate that MHBA treatment of enteroendocrine cells increases Ca2+ levels and induces the secretion of the gastrointestinal hormone, cholecystokinin (CCK), in a dose-dependent manner. These effects were eliminated by Ca2+ depletion from the medium or blockers of L-type voltage-sensitive Ca2+ channels during pretreatment. Induction of CCK secretion by MHBA was also confirmed using isolated rat small intestines. Elevation of the sympathetic nerve activity innervating BAT (BAT-SNA) and BAT temperature by MHBA administration in rats was blocked by pretreatment with a CCK receptor 1 (CCK1R) antagonist. Moreover, the intraperitoneal injection of CCK fragment elevated BAT-SNA, and this increase was blocked by subdiaphragmatic vagotomy. These results demonstrate that MHBA induces CCK secretion in the gastrointestinal tracts and elevates BAT-SNA via CCK1R and vagal afferent nerves. In addition, MHBA increases BAT temperature via CCK1R. Our findings reveal a novel mechanism of the beneficial metabolic effects of food ingredients.

2-Ethylpyrazine Induces Vasodilatation by Releasing Nitric Oxide in the Endothelium.

Oxygen transportation and regulation of some physiological processes are facilitated by blood flow. Furthermore, blood flow is regulated by various factors such as nitric oxide (NO) and the autonomic nerve system. In modern life, many people suffer from chilliness (hiesho) because of mental stress and an excessive use air-conditioning systems, which induces vasoconstriction in the peripheral skin. In this study, we focused on pyrazine derivatives, particularly compounds that are used as food flavoring materials, and investigated their effects on vascular function and blood flow. We examined the vasodilatory effect of pyrazine derivatives in the rat thoracic aorta and found 2-ethylpyrazine (2-EP) to be the most active pyrazine compound. Additionally, we found that 2-EP induces vasodilatation through the activities of endothelium-derived relaxing factors. 2-EP activates NO synthesis through the effect of endothelial NO synthase in the endothelium. As a result, cyclic GMP levels rise in smooth muscle cells and vasodilatation is induced. We also confirmed that 2-EP increases peripheral blood flow in rats. From these results, we concluded that 2-EP induces vasodilatation by inducing the release of NO and increasing peripheral blood flow.

Matured hop extract reduces body fat in healthy overweight humans: a randomized, double-blind, placebo-controlled parallel group study.

BACKGROUND: Hops are the main components of beer that provide flavor and bitterness. Iso-α-acids, the bitter components of beer, have been reported to reduce body fat in humans, but the bitterness induced by effective doses of iso-α-acids precludes their acceptance as a nutrient. The matured hop bitter acids (MHBA) of oxidized hops appear to have a more pleasant bitterness compared to the sharper bitterness of iso-α-acids. While there has been little information concerning the identity of the MHBA compounds and their physiological effects, MHBA was recently found to be primarily composed of oxides derived from α-acids, and structurally similar to iso-α-acids. Here, we investigated the effects of matured hop extract (MHE) containing MHBA on reducing abdominal body fat in healthy subjects with a body mass index (BMI) of 25 to below 30 kg/m(2), classified as "obese level 1" in Japan or as "overweight" by the WHO. TRIAL DESIGN: A randomized, double-blind, placebo-controlled parallel group study. METHODS: Two hundred subjects (male and female aged 20 to below 65 years with a BMI of 25 or more and less than 30 kg/m(2)) were randomly assigned to two groups. During a 12-week ingestion period, the subjects in each group ingested daily 350 mL of test-beverage, either containing MHE (with 35 mg MHBA), i.e. the namely active beverage, or a placebo beverage without MHE. The primary endpoint was reduction of the abdominal fat area as determined by CT scanning after continual ingestion of MHE for 12 weeks. RESULTS: Compared to the placebo group, a significant reduction was observed in the visceral fat area after 8 and 12 w, and in the total fat area after 12 w in the active group. There was also a concomitant decrease in body fat ratio in the active group compared to the placebo group. No adverse events related to the test beverages or clinically relevant abnormal changes in the circulatory, blood and urine parameters were observed in either group. CONCLUSIONS: The present study suggests that continual ingestion of MHE safely reduces body fat, particularly the abdominal visceral fat of healthy overweight subjects. TRIAL REGISTRATION: UMIN-CTR UMIN000014185.