Abstract
BackgroundLipid accumulation is the primary evidence of non-alcoholic fatty liver disease (NAFLD). Ginkgo biloba extract (GBE) and its flavonoid ingredients (quercetin, kaempferol, and isorhamnetin) could lessen the lipid accumulation associated with up-regulation of the rate-limiting enzyme, carnitine palmitoyltransferase 1A (CPT1A), in the β-oxidation of long-chain fatty acids. In this study, we investigated the mechanisms by which GBE and its flavonoids induced expression of CPT1A.ResultsCPT1A inhibition with RNAi resulted in triglyceride accumulation in HepG2 cells. Through deletion and mutation analysis of CPT1A’s promoter combined with electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments, the CPT1A promoter region (−50 to −5 nt) was determined to contain two putative Sp1 binding sites, namely Sp1a and Sp1b, which might act as the GBE regulation response DNA element. Sp1 might be induced to transfer from cytoplasma to nucleus to bind the promoter region of −50 to −5 nt by GBE. The regulatory effects of GBE on CPT1A were also verified on the flavonoid ingredients quercetin, kaempferol, and isorhamnetin.ConclusionSp1 was crucial in regulating CPT1A expression with GBE and its flavonoid ingredients, and the −50 to −5 nt region of CPT1A promoter played important roles in Sp1 binding.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-014-0087-x) contains supplementary material, which is available to authorized users.
Highlights
Lipid accumulation is the primary evidence of non-alcoholic fatty liver disease (NAFLD)
Our results revealed an Sp1 binding region located in the carnitine palmitoyltransferase 1A (CPT1A) promoter was critical for the regulation of CPT1A by Ginkgo biloba extract (GBE)
We observed a significant up-regulation of CPT1A by GBE in negative control (NC) group cells when GBE or the flavonoids were added after transfection for 24 hours, while no influence was shown in the group silenced by shRNA1
Summary
Lipid accumulation is the primary evidence of non-alcoholic fatty liver disease (NAFLD). Ginkgo biloba extract (GBE) and its flavonoid ingredients (quercetin, kaempferol, and isorhamnetin) could lessen the lipid accumulation associated with up-regulation of the rate-limiting enzyme, carnitine palmitoyltransferase 1A (CPT1A), in the β-oxidation of long-chain fatty acids. Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride (TG) accumulation in hepatocytes and is commonly associated with dyslipidemia, hypertension, obesity, and hyperglycemia. Ginkgo biloba extract (GBE) mainly consists of two groups of active components: flavonoid and terpenoid [3]. GBE, with its flavonoid ingredients, could significantly up-regulate expression of carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in the β-oxidation of long-chain fatty acids (LCFAs), and elevate its activity [4,5]. The mechanisms of regulation in CPT1A expression remained uncertain
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