Abstract

Lipid metabolism disorder is one of the significant risk factors for a multitude of human diseases and has become a serious threat to human health. The present study aimed to evaluate the effects of phenolics from poplar-type propolis on regulating lipid metabolism by using cell models of steatosis induced by palmitic acid (PA). Our study shows that phenolic esters have higher lipid-lowering activities than phenolic acids, especially for three caffeic acid esters, including caffeic acid phenethyl ester (CAPE), caffeic acid cinnamyl ester (CACE), and caffeic acid benzyl ester (CABE). Most notably, CACE presents prominent properties to prevent intracellular lipid accumulation and to amend extracellular adipokine secretion abnormalities. In addition, our results firstly reveal that CACE can alleviate lipid metabolism disorder through mediating protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6) signaling pathway-associated protein expression, suppressing endoplasmic reticulum (ER) stress, and activating peroxisome proliferator-activated receptors (PPARs) by distinct upregulation of PPARα and downregulation of PPARγ.

Highlights

  • At present, nearly one billion adults worldwide are overweight, and at least 300 million are obesity, especially in Europe, North America, and a large number of developing nations

  • Bicinchoninic acid (BCA) protein assay kit, dimethyl sulfoxide (DMSO), 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-Htetrazolium bromide (MTT), palmitic acid (PA), fenofibric acid (FFBA), tauroursodesoxycholic acid (TUDCA), Oil Red O, paraformaldehyde, hematoxylin, isobutyl methyl xanthine (IBMX), dexamethasone, and insulin were obtained from Sigma-Aldrich

  • Multifactor assay kits containing adiponectin, interleukin-6 (IL-6), leptin, monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor-alpha (TNF-α) was purchased from Merck Millipore (Darmstadt, Germany). β-Actin antibody, CCAAT/enhancer-binding protein homologous protein (CHOP) antibody, activating transcription factor-6α (ATF6α) antibody, inositol-requiring protein1α (IRE1α) antibody, activating peroxisome proliferatoractivated receptor-α (PPARα) antibody, PPARβ/δ antibody, and PPARc antibody were purchased from Abcam (Cambridge, MA, USA)

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Summary

Introduction

Nearly one billion adults worldwide are overweight, and at least 300 million are obesity, especially in Europe, North America, and a large number of developing nations. Hypertension [1], diabetes [2], and cardiovascular disease [3] are seriously threatening human health with rising morbidity and mortality rates. Given to these health issues, many researchers have been alarmed that obesity can be driven by a high and growing prevalence of metabolic syndrome [4, 5]. To alleviate lipid metabolism disorder, many drugs have been proved to be an effective approach. Long-term use of these drugs can cause statin intolerance and adverse effects, such as gastrointestinal upset, chronic muscle disease, hepatitis, and liver cell damage [12, 13]

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