Abstract

This study investigated the effects of indole-3-carbinol (I3C) on adipogenesis- and angiogenesis-associated factors in mature adipocytes. The cross-talk between mature adipocytes and endothelial cells (ECs) was also explored by cultivating ECs in a conditioned medium (CM) by using I3C-treated adipocytes. The results revealed that I3C significantly inhibited triglyceride accumulation in mature adipocytes in association with significantly increased expression of AhR and CYP1B1 proteins as well as slightly decreased nuclear factor erythroid-derived factor 2–related factor 2, hormone-sensitive lipase, and glycerol-3-phosphate dehydrogenase expression by mature adipocytes. Furthermore, I3C inhibited CM-stimulated endothelial tube formation, which was accompanied by the modulated secretion of angiogenic factors in adipocytes, including vascular endothelial growth factor, interleukin-6, matrix metalloproteinases, and nitric oxide. In conclusion, I3C reduced lipid droplet accumulation in adipocytes and suppressed adipocyte-stimulated angiogenesis in ECs, suggesting that I3C is a potential therapeutic agent for treating obesity and obesity-associated disorders.

Highlights

  • Obesity has been a major concern since the 20th century, and its prevalence is increasing in many countries

  • Mature adipocytes are a lipid storage site and produce and secrete different adipokines and factors such as leptin, interleukin (IL)-6, and vascular endothelial growth factor (VEGF), which are closely associated with angiogenesis and other pathological conditions in obesity [2,3]

  • I3C and the AhR antagonist antagonist α-naphthoflavone (ANF) suppressed Nrf-2 protein expression in mature adipocytes. These results suggest that Nrf-2 predominantly affects adipocyte differentiation; it either does not regulate or only slightly regulates AhR expression and angiogenesis in mature adipocytes

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Summary

Introduction

Obesity has been a major concern since the 20th century, and its prevalence is increasing in many countries. In addition to mature adipocytes, WAT consists of fibroblastic preadipocytes, endothelial cells (ECs), and macrophages. The expansion of mature adipoctyes, the differentiation of preadiopocytes to adipocytes, the formation of new vessels of ECs, and the infiltration of macrophages accompany the progress of WAT expansion in obesity [2]. Mature adipocytes are a lipid storage site and produce and secrete different adipokines and factors such as leptin, interleukin (IL)-6, and vascular endothelial growth factor (VEGF), which are closely associated with angiogenesis and other pathological conditions in obesity [2,3]. Effects of I3C on Adipocyte-Induced Tube Formation in ECs. Expansion of adipose tissue is accompanied by increased endothelial angiogenesis; enEdxopthaenlisailotnuboef afodrimpoastieontiswsuase uisseadcctoomepxpalnoireedthbey einffcercetsasoefdI3eCndoonthinetleiaralcatniognisogbentweseiesn; tmheartuefroere, endadoitphoecliyatlestuabnedfoErCmsa. EEffffeeccttss ooff II33CC oonn PPrrootteeiinn EExxpprreessssiioonn bbyy MMaattuurree AAddiippooccyytteess.

Discussion
Chemicals and Biochemicals
Cell Culture
Cytotoxicity
Lipid Accumulation and Glycerol Release of 3T3-L1 Adipocyte
Tube Formation Assay
Western Blot Analysis
Statistical Analysis
Findings
Conclusions
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