Inhibitory activity of diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP) by the flavonoid, taxifolin, in HepG2 cells: potential role in the regulation of apolipoprotein B secretion

Casaschi, Adele; Rubio, Brent K.; Maiyoh, Geoffrey K.; Theriault, André

doi:10.1016/j.atherosclerosis.2004.05.020

Cited by 54 publications

(31 citation statements)

References 22 publications

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“…The results of the present study also indicate that PJ or punicalagin regulate DGAT1 posttranscriptionally at the activity level. Similarly to the results observed in the current study, it has been shown that quercetin inhibits DGAT1 activity in CaCo2 cells [42] and that taxifolin inhibits triglyceride biosynthesis in HepG2 cells as a result of a noncompetitive type of DGAT1 inhibition [43]. Furthermore, the suppression of DGAT1 activity by taxifolin is due to a posttranscriptional mechanism of action [43].…”

Section: Discussionsupporting

confidence: 57%

Pomegranate Juice Protects Macrophages from Triglyceride Accumulation: Inhibitory Effect on DGAT1 Activity and on Triglyceride Biosynthesis

Rosenblat

Aviram²

2011

Ann Nutr Metab

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Background/Aims: To analyze the effects of pomegranate juice (PJ) and punicalagin on macrophage triglyceride metabolism. Methods: Triglyceride metabolism was analyzed in PJ- or punicalagin-treated J774A.1 macrophages or in mouse peritoneal macrophages (MPM) harvested from C57BL/6 mice or from paraoxonase 2 (PON2)-deficient mice. Results: PJ (0–50 µM) significantly and dose-dependently decreased the triglyceride content and triglyceride biosynthesis rate in J774A.1 macrophages or in C57BL/6 MPM by about 30%. Similarly, punicalagin, the major PJ polyphenol, inhibited the MPM triglyceride biosynthesis rate by 40%. The triglyceride hydrolytic rate, however, was not significantly affected by PJ or punicalagin. The activity of diacylglycerol acyltransferase 1 (DGAT1; the rate-limiting enzyme in triglyceride biosynthesis) was significantly inhibited, by 54%, in C57BL/6 MPM that were treated with 50 µM PJ or punicalagin, with no significant effect on DGAT1 mRNA or protein expression. Both PJ and punicalagin increased (1.7-fold) MPM PON2 mRNA expression, and PON2 was previously shown to inhibit DGAT1 activity. However, the addition of PJ or punicalagin (50 µM) to microsomes from PON2-deficient MPM still resulted in a significant reduction (50–58%) in DGAT1 activity. Conclusions: We conclude that the inhibitory effect of PJ on triglyceride biosynthesis could be attributed to a direct effect of PJ on DGAT1 activity.

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Section: Discussionsupporting

confidence: 57%

Pomegranate Juice Protects Macrophages from Triglyceride Accumulation: Inhibitory Effect on DGAT1 Activity and on Triglyceride Biosynthesis

Rosenblat

Aviram²

2011

Ann Nutr Metab

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“…Taxifolin can effectively prevent osmotic stress in hyperglycemia, decrease the tetracycline and tetrachloride methane-induced lipid peroxidation of liver microsome, and reduce the content of low-density lipoproteins in liver and serum [5][6][7][8]. It has been found that taxifolin can help to provide essential neuroprotection against the free-radicalinduced oxidative damage that often occurs when the brain does not receive enough blood and oxygen [9].…”

Section: Introductionmentioning

confidence: 99%

A highly sensitive and robust UPLC–MS with electrospray ionization method for quantitation of taxifolin in rat plasma

Wang

Xia

Feng

et al. 2009

Journal of Chromatography B

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“…8 Among them, acyl-CoA: diacylglycerol acyltransferase (DGAT) 9 is the final enzyme to synthesize TG, and only a few DGAT inhibitors have been reported by several groups, including ours. [10][11][12][13][14] We established a high-content assay to observe the TG biosynthetic pathway using intact CHO-K1 cells. During our screening for the inhibitors of TG synthesis using this cell-based assay, new biaryl dihydronaphthopyranones, named dinapinone (Figure 1), were isolated from the culture broth of Penicillium pinophilum FKI-3864.…”

Section: Introductionmentioning

confidence: 99%

Dinapinones, novel inhibitors of triacylglycerol synthesis in mammalian cells, produced by Penicillium pinophilum FKI-3864

et al. 2011

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Dinapinone A, a novel biaryl dihydronaphthopyranone, was isolated from the culture broth of Penicillium pinophilum FKI-3864 by solvent extraction, silica gel and ODS column chromatography and HPLC. Dinapinone A showed very potent inhibition of triacylglycerol (TG) synthesis in intact Chinese hamster ovary K1 (CHO-K1) cells with an IC 50 value of 0.097 lM. Dinapinone A was found to be a mixture of stereoisomers, resulting in its separation into dinapinones A1 and A2 by HPLC using a C30 reverse-phase column. Dinapinone A1 did not inhibit TG synthesis in CHO-K1 cells even at 12 lM, and dinapinone A2 showed less potent inhibition (IC 50 ; 0.65 lM) than dinapinone A; however, a mixture of isolated dinapinones A1 and A2 (a 1:1 ratio) recovered the potent TG inhibitory activity (IC 50 ; 0.054 lM). A similar effect of dinapinone on TG synthesis in intact Raji cells was also observed.

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Inhibitory activity of diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP) by the flavonoid, taxifolin, in HepG2 cells: potential role in the regulation of apolipoprotein B secretion

Cited by 54 publications

References 22 publications

Pomegranate Juice Protects Macrophages from Triglyceride Accumulation: Inhibitory Effect on DGAT1 Activity and on Triglyceride Biosynthesis

Pomegranate Juice Protects Macrophages from Triglyceride Accumulation: Inhibitory Effect on DGAT1 Activity and on Triglyceride Biosynthesis

A highly sensitive and robust UPLC–MS with electrospray ionization method for quantitation of taxifolin in rat plasma

Dinapinones, novel inhibitors of triacylglycerol synthesis in mammalian cells, produced by Penicillium pinophilum FKI-3864

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