Abstract

Hypertrophic obesity inhibits activation of peroxisome proliferators-activated receptor gamma (PPARγ), considered the key mediator of the fully differentiated and insulin sensitive adipocyte phenotype. We examined the effects of Caffeic Acid Phenethyl Ester (Cape), isolated from propolis, a honeybee hive product, on Adipose Stem Cells (ASCs) differentiation to the adipocyte lineage. Finally we tested the effects of Cape on insulin-resistant adipocytes. Quantification of Oil Red O-stained cells showed that lipid droplets decreased following Cape treatment as well as radical oxygen species formation. Additionally, exposure of ASC to high glucose levels decreased adiponectin and increased proinflammatory cytokines mRNA levels, which were reversed by Cape-mediated increase of insulin sensitivity. Cape treatment resulted in decreased triglycerides synthesis and increased beta-oxidation. Exposure of ASCs to Lipopolysaccharide (LPS) induced a reduction of PPARγ, an increase of IL-6 levels associated with a well-known stimulation of lipolysis; Cape partially attenuated the LPS-mediated effects. These observations reveal the main role of PPARγ in the adipocyte function and during ASC differentiation. As there is now substantial interest in functional food and nutraceutical products, the observed therapeutic value of Cape in insulin-resistance related diseases should be taken into consideration.

Highlights

  • White adipose tissue is constituted by different cellular types including preadipocytes, mature adipocytes, fibroblasts, pericytes, macrophages, neutrophils, lymphocytes, endothelial cells, and Adipose Stem Cells (ASCs)

  • We examined the effects of Caffeic Acid Phenethyl Ester (Cape), isolated from propolis, a honeybee hive product, on Adipose Stem Cells (ASCs) differentiation to the adipocyte lineage

  • Adipocytes produce a variety of molecules biologically active including interleukins, tumor necrosis factor-alpha (TNF-α), resistin, leptin, adiponectin, monocyte chemoattractant protein- (MCP-) 1, transforming growth factor(TGF-) β, insulin-like growth factor- (IGF-) 1, and C-reactive protein (CRP); a deregulated production of these factors is involved in the systemic inflammatory process occurring in obesity [2, 3]

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Summary

Introduction

White adipose tissue is constituted by different cellular types including preadipocytes, mature adipocytes, fibroblasts, pericytes, macrophages, neutrophils, lymphocytes, endothelial cells, and Adipose Stem Cells (ASCs). The balance between these different cell types and their expression profile is closely related to maintenance of the organ metabolic function [1]. Adipose tissue expresses numerous receptors that allow it to respond to afferent signals from traditional hormone systems as well as the central nervous system; adipose organ mediates numerous physiological and pathological processes by factors that control glucose metabolism, appetite, immunological responses, inflammatory responses, angiogenesis, blood pressure regulation, and reproductive function. Adipose tissue expansion is associated with adipocyte dysfunction and increased inflammatory processes

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