title: Diosgenin, the main aglycon of fenugreek, inhibits LXRα activity in HepG2 cells and decreases plasma and hepatic triglycerides in obese diabetic mice.
abstract: Trigonella foenum-graecum (fenugreek) can ameliorate dyslipidemia, but the detailed mechanism is unclear. In this study, we examined the effects of fenugreek on hepatic lipid metabolism, particularly lipogenesis, which is enhanced in obesity and diabetes, in diabetic obese KK-Ay mice. KK-Ay mice were fed a control high-fat diet (HFD; 60% of energy as fat) (C group) or an HFD containing 0.5% or 2% fenugreek (0.5F and 2.0F groups, respectively) for 4 wk. Hepatic and plasma TG and mRNA expression levels of lipogenic genes were lower in the 2.0F group at 4 wk (P < 0.05), but not in the 0.5F group, than in the C group. The hydrolyzed saponin fraction, but not the saponin fraction per se, in fenugreek inhibited the accumulation of TG in HepG2 cells. We fractionated the hydrolyzed saponin into 15 fractions by HPLC and examined the effect of these fractions on TG accumulation in HepG2 cells. Fraction 11 inhibited TG accumulation in HepG2 cells and we determined by liquid chromatography tandem MS that the active substance contained in fraction 11 is diosgenin. Diosgenin (5 and 10 μmol/L) inhibited the accumulation of TG and the expression of lipogenic genes in HepG2 cells. Moreover, diosgenin inhibited the transactivation of liver-X-receptor-α, as measured using a luciferase assay system and by gel mobility shift assay. These findings suggest that fenugreek ameliorates dyslipidemia by decreasing the hepatic lipid content in diabetic mice and that its effect is mediated by diosgenin. Fenugreek, which contains diosgenin, may be useful for the management of diabetes-related hepatic dyslipidemias.
authors.affiliation: Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Uemura
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.forename: Min-Sook
authors.initials: MS
authors.lastname: Kang
authors.forename: Noriko
authors.initials: N
authors.lastname: Mizoguchi
authors.forename: Shizuka
authors.initials: S
authors.lastname: Hirai
authors.forename: Joo-Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakano
authors.forename: Jinji
authors.initials: J
authors.lastname: Shono
authors.forename: Shohei
authors.initials: S
authors.lastname: Hoshino
authors.forename: Keiko
authors.initials: K
authors.lastname: Taketani
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tsuge
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Narukami
authors.forename: Makoto
authors.initials: M
authors.lastname: Makishima
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D004144:Diosgenin / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008820:Mice, Obese; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors*; D008517:Phytotherapy; D012333:RNA, Messenger / Q000032:analysis; D051780:Sterol Regulatory Element Binding Protein 1 / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism*; D029910:Trigonella / Q000737:chemistry*
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D004144:Diosgenin