title: Oleuropein aglycone enhances UCP1 expression in brown adipose tissue in high-fat-diet-induced obese rats by activating β-adrenergic signaling.
abstract: Oleuropein is the pungent principle of raw olives. Oleuropein aglycone (OA) is a major phenolic compound in extra virgin olive oil and the absorbed form of oleuropein. We aimed to determine the mechanism underlying the nutritional effects of oleuropein and OA on interscapular brown adipose tissue (IBAT) in rats with high-fat (HF) diet-induced obesity by examining the agonistic activity of oleuropein and OA toward the transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1). Four-week-old male Sprague-Dawley rats were fed an HF (palm oil 30% wt:wt) diet alone or with oleuropein (HF-O, 1 g/kg diet) for 28 days. In rats fed HF-O compared to HF, urinary noradrenaline, adrenaline and UCP1 levels in IBAT were significantly higher, whereas plasma leptin levels and the total weight of the abdominal cavity adipose tissue were significantly lower. In anaesthetized 7-week-old male Sprague-Dawley rats, the OA (3.8 mg of intravenous injection)-induced increase in plasma noradrenaline secretion was suppressed by TRPA1 or TRPV1 antagonist and by a β2- or β3-adrenoceptor antagonist. Furthermore, OA-activated rat and human TRPV1s expressed on HEK293 cells at the same level as zingerone (pungent component in ginger). OA also activated humanTRPA1, and its potency was approximately 10-fold stronger than that for TRPV1. These findings suggest that OA is the agonist of both TRPA1 and TRPV1 and that OA enhances UCP1 expression in IBAT with a concomitant decrease in the visceral fat mass of HF-diet-induced obese rats through enhanced noradrenaline secretion via β-adrenergic action following TRPA1 and TRPV1 activation.
authors.affiliation: Laboratory of Nutrition Chemistry, Faculty of Home Economics, Kobe Women's University, Suma, Kobe, Japan. Electronic address: oi@suma.kobe-wu.ac.jp.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Oi-Kano
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: School of Food and Nutritional Sciences, University of Shizuoka, Suruga, Shizuoka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: School of Food and Nutritional Sciences, University of Shizuoka, Suruga, Shizuoka, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
authors.affiliation: J-Oil Mills Inc., Yokohama, Kanagawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Laboratory of Nutrition Chemistry, Faculty of Home Economics, Kobe Women's University, Suma, Kobe, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Iwai
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D000081004:Cyclopentane Monoterpenes; D059305:Diet, High-Fat / Q000009:adverse effects; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D000074025:TRPA1 Cation Channel / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000378:metabolism*
chemical_list: D000085:Acetates; D002395:Catecholamines; D000081004:Cyclopentane Monoterpenes; D057888:Iridoid Glucosides; D039823:Iridoids; D011714:Pyrans; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C000625725:oleuropein aglycone; C002769:oleuropein; D009638:Norepinephrine; D004837:Epinephrine
keywords: Brown adipose tissue; Noradrenaline; Oleuropein aglycone; TRPA1; TRPV1; Uncoupling protein 1