Abstract
Neochlorogenic acid (5-Caffeoylquinic acid; 5-CQA), a major phenolic compound isolated from mulberry leaves, possesses anti-oxidative and anti-inflammatory effects. Although it modulates lipid metabolism, the molecular mechanism is unknown. Using an in-vitro model of nonalcoholic fatty liver disease (NAFLD) in which oleic acid (OA) induced lipid accumulation in HepG2 cells, we evaluated the alleviation effect of 5-CQA. We observed that 5-CQA improved OA-induced intracellular lipid accumulation by downregulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression, which regulates the fatty acid synthesis, as well as SREBP2 and HMG-CoA reductases (HMG-CoR) expressions, which regulate cholesterol synthesis. Treatment with 5-CQA also increased the expression of fatty acid β-oxidation enzymes. Remarkably, 5-CQA attenuated OA-induced miR-34a expression. A transfection assay with an miR-34a mimic or miR-34a inhibitor revealed that miR-34a suppressed Moreover, Sirtuin 1 (SIRT1) expression and inactivated 5’ adenosine monophosphate-activated protein kinase (AMPK). Our results suggest that 5-CQA alleviates lipid accumulation by downregulating miR-34a, leading to activation of the SIRT1/AMPK pathway.
Highlights
The liver is the main organ controlling cholesterol and fatty acid metabolism
To identify the mechanisms involved in the reduction of hepatic lipid accumulation by 5-CQA, we investigated the expression of lipogenic proteins including sterol regulatory element-binding proteins (SREBPs), fatty acid synthase (FASN), and HMG-CoA reductases (HMG-CoR)
Dysregulation of lipid metabolism leading to excessive lipid accumulation in the liver is a major risk factor for development of life-threatening diseases such as nonalcoholic fatty liver disease (NAFLD)
Summary
The liver is the main organ controlling cholesterol and fatty acid metabolism. Excessive lipid accumulation in the liver is associated with several diseases, such as diabetes, atherosclerosis, and NAFLD [1]. SREBP1 activates the transcription of genes required for fatty acid and fatty acid synthesis; SREBP2 modulates the transcription of genes required for cholesterol synthesis [4,5]. It is directly or indirectly modulated by AMPK, an energy-sensing protein complex, to regulate the process of lipid homeostasis [6,7]. SIRT1, a nicotinamide adenine dinucleotide-dependent deacetylase, may be required for AMPK activation and the regulation of the transcriptional network of cellular lipid metabolism involved in NAFLD progression [8]. The SIRT1/AMPK pathway is one of the promising targets in NAFLD prevention
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