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

Takahiro Yamazaki, Yumie Morimoto-Kobayashi, Kumiko Koizumi, Chika Takahashi, Shiori Nakajima, Sayoko Kitao, Yoshimasa Taniguchi, Mikio Katayama, Yoshihiro Ogawa

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)80-87
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume64
DOIs
Publication statusPublished - Feb 2019

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Gastrointestinal Hormones
Humulus
Brown Adipose Tissue
Cholecystokinin
Tissue
Acids
Rats
Cholecystokinin Receptors
Beer
Enteroendocrine Cells
Flavors
Food
Neurology
Temperature
Thermogenesis
Vagotomy
Sympathetic Nervous System
Intraperitoneal Injections
Small Intestine
Gastrointestinal Tract

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Secretion of a gastrointestinal hormone, cholecystokinin, by hop-derived bitter components activates sympathetic nerves in brown adipose tissue. / Yamazaki, Takahiro; Morimoto-Kobayashi, Yumie; Koizumi, Kumiko; Takahashi, Chika; Nakajima, Shiori; Kitao, Sayoko; Taniguchi, Yoshimasa; Katayama, Mikio; Ogawa, Yoshihiro.

In: Journal of Nutritional Biochemistry, Vol. 64, 02.2019, p. 80-87.

Research output: Contribution to journalArticle

Yamazaki, Takahiro ; Morimoto-Kobayashi, Yumie ; Koizumi, Kumiko ; Takahashi, Chika ; Nakajima, Shiori ; Kitao, Sayoko ; Taniguchi, Yoshimasa ; Katayama, Mikio ; Ogawa, Yoshihiro. / Secretion of a gastrointestinal hormone, cholecystokinin, by hop-derived bitter components activates sympathetic nerves in brown adipose tissue. In: Journal of Nutritional Biochemistry. 2019 ; Vol. 64. pp. 80-87.
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