Mechanism of the fungal-like particles in the inhibition of adipogenesis in 3T3-L1 adipocytes

Chanawee Jakkawanpitak,Ruthaiwan Bunkrongcheap,Masashi Inafuku,Hirosuke Oku,Decha Sermwittayawong,Nongporn Hutadilok-Towatana,Natthawan Sermwittayawong,Piyapat Aiemchareon

doi:10.1038/s41598-021-98385-y

Chanawee Jakkawanpitak, Ruthaiwan Bunkrongcheap + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-98385-y

Copy DOI

Abstract

The dynamic ability of adipocytes in adipose tissue to store lipid in response to changes in the nutritional input and inflammatory elicitors has a major impact on human health. Previously, we established laminarin-coated beads or LCB as an inflammatory elicitor for adipocytes. However, it was not clear whether LCB inhibits lipid accumulation in adipocytes. Here, we show that LCB acts in the early stage of adipogenesis through both interleukin-1 receptor-associated kinases (IRAK) and spleen tyrosine kinase (SYK) pathways, resulting in the activation of the AMP-activated protein kinase (AMPK) and nuclear factor-κB (NF-κB) complexes, which subsequently cause cell cycle arrest, downregulation of the key transcription factors and enzymes responsible for adipogenesis, inhibition of adipogenesis, and stimulation of an inflammatory response. While LCB could effectively block lipid accumulation during the early stage of adipogenesis, it could stimulate an inflammatory response at any stage of differentiation. Additionally, our results raise a possibility that toll-like receptor 2 (TLR2) and C-type lectin domain family 7 member A (CLEC7A/Dectin-1) might be potential β-glucan receptors on the fat cells. Together, we present the mechanism of LCB, as fungal-like particles, that elicits an inflammatory response and inhibits adipogenesis at the early stage of differentiation.

Highlights

The dynamic ability of adipocytes in adipose tissue to store lipid in response to changes in the nutritional input and inflammatory elicitors has a major impact on human health
The results show that the percentage of lipid accumulation in the laminarin‐coated beads (LCB)-treated differentiating adipocytes decreases as the amount of LCB added to the cells increases (Fig. 1E–H), suggesting that LCB dose-dependently inhibits adipogenesis
The uncoated beads (UC)-treated differentiating adipocytes reveal a comparable level of lipid accumulation with the untreated set (Fig. 1C,H), suggesting that the effect of LCB was conferred by laminarin (β-glucan) on the beads but not the beads themselves

Summary

Introduction

The dynamic ability of adipocytes in adipose tissue to store lipid in response to changes in the nutritional input and inflammatory elicitors has a major impact on human health. While LCB could effectively block lipid accumulation during the early stage of adipogenesis, it could stimulate an inflammatory response at any stage of differentiation. IBMX, a synthetic glucocorticoid, stimulates the glucocorticoid pathways and activates CCAAT/enhancer-binding protein beta (C/ebpβ) gene expression, whereas dexamethasone/ DEX upregulates the C/ebpδ gene expression[3] The expression of both C/EBPβ and C/EBPδ marks the early stage of adipogenesis. It was shown that high-molecular-weight barley β-glucan suppressed lipid accumulation in 3T3-L1 adipocytes by downregulating both mRNAs and proteins of the key adipogenesis transcription factors such as PPARγ and C/EBPα6. These data suggest that there must be a specific β-glucan receptor on the surface of the cells

Methods

Results

Conclusion