Kudinoside-D, a triterpenoid saponin derived from Ilex kudingcha suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes

Che, Yanyun; Wang, Qiuhong; Xiao, Rui-Chun; Zhang, Jiayu; Zhang, Yaqiong; Gu, Wen; Rao, G. Venkata; Wang, Changfu; Kuang, Hai‐Xue

doi:10.1016/j.fitote.2017.11.018

Cited by 20 publications

(16 citation statements)

References 29 publications

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“…To measure triglyceride contents, stained adipocytes were eluted with isopropanol for 20 min. The optical density values were detected with a spectrophotometer at a wavelength of 510 nm, as described previously (18).…”

Section: Oil Red O Stainingmentioning

confidence: 99%

Melatonin reduces intramuscular fat deposition by promoting lipolysis and increasing mitochondrial function

Liu¹,

Yu²,

Wei

et al. 2019

Journal of Lipid Research

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Section: Oil Red O Stainingmentioning

confidence: 99%

Melatonin reduces intramuscular fat deposition by promoting lipolysis and increasing mitochondrial function

Liu¹,

Yu²,

Wei

et al. 2019

Journal of Lipid Research

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“…Adipogenic differentiation and myogenic differentiation are essential developmental processes of adipose and skeletal muscle, regulated by complex molecular networks and epigenetic modifications 8 - 11 . Adipogenesis and myogenesis marker genes (e.g., PPARG , CEBPA , and FABP4 in adipocytes, and MRFs and MHC in myotubes) were shown to be activated during differentiation, accompanied by changes in cell morphology (lipid droplet accumulation of adipocytes and fusion of myoblasts into multinucleated myotubes, respectively) 12 , 13 . Adipogenesis- and myogenesis-associated expression of PPARG and FRG1 was found to be regulated by long-range chromatin interactions, respectively, suggesting the modulatory role of spatial chromatin structure in adipogenesis and myogenesis 14 , 15 .…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis

He¹,

Li²,

Tang³

et al. 2018

Int. J. Biol. Sci.

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The recently developed high-throughput chromatin conformation capture (Hi-C) technology enables us to explore the spatial architecture of genomes, which is increasingly considered an important regulator of gene expression. To investigate the changes in three-dimensional (3D) chromatin structure and its mediated gene expression during adipogenesis and myogenesis, we comprehensively mapped 3D chromatin organization for four cell types (3T3-L1 pre-adipocytes, 3T3-L1-D adipocytes, C2C12 myoblasts, and C2C12-D myotubes). We demonstrate that the dynamic spatial genome architecture affected gene expression during cell differentiation. A considerable proportion (~22%) of the mouse genome underwent compartment A/B rearrangement during adipogenic and myogenic differentiation, and most (~80%) upregulated marker genes exhibited an active chromatin state with B to A switch or stable A compartment. More than half (65.4%-73.2%) of the topologically associating domains (TADs) are dynamic. The newly formed TAD and intensified local interactions in the Fabp gene cluster indicated more precise structural regulation of the expression of pro-differentiation genes during adipogenesis. About half (32.39%-59.04%) of the differential chromatin interactions (DCIs) during differentiation are promoter interactions, although these DCIs only account for a small proportion of genome-wide interactions (~9.67% in adipogenesis and ~4.24% in myogenesis). These differential promoter interactions were enriched with promoter-enhancer interactions (PEIs), which were mediated by typical adipogenic and myogenic transcription factors. Differential promoter interactions also included more differentially expressed genes than nonpromoter interactions. Our results provide a global view of dynamic chromatin interactions during adipogenesis and myogenesis and are a resource for studying long-range chromatin interactions mediating the expression of pro-differentiation genes.

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“…As a result, it was confirmed by Oil Red O staining that SSA and SSD suppressed lipid accumulation without decreasing cell viability in a dose-dependent manner. Numerous studies have reported that various natural triterpenoid saponins inhibit adipogenesis and downregulate the cellular lipid accumulation of ginsenoside Rb1 [ 27 ], ginsenoside Rh1 [ 28 ], ursolic acid [ 29 ], and kudinoside-D [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Saikosaponin A and D Inhibit Adipogenesis via the AMPK and MAPK Signaling Pathways in 3T3-L1 Adipocytes

Lim

Lee

Han

et al. 2021

IJMS

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Obesity is a lipid metabolism disorder caused by genetic, medicinal, nutritional, and other environmental factors. It is characterized by a complex condition of excess lipid accumulation in adipocytes. Adipogenesis is a differentiation process that converts preadipocytes into mature adipocytes and contributes to excessive fat deposition. Saikosaponin A (SSA) and saikosaponin D (SSD) are triterpenoid saponins separated from the root of the Bupleurum chinensis, which has long been used to treat inflammation, fever, and liver diseases. However, the effects of these constituents on lipid accumulation and obesity are poorly understood. We investigated the anti-obesity effects of SSA and SSD in mouse 3T3-L1 adipocytes. The MTT assay was performed to measure cell viability, and Oil Red O staining was conducted to determine lipid accumulation. Various adipogenic transcription factors were evaluated at the protein and mRNA levels by Western blot assay and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Here, we showed that SSA and SSD significantly inhibited lipid accumulation without affecting cell viability within the range of the tested concentrations (0.938–15 µM). SSA and SSD also dose-dependently suppressed the expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), sterol regulatory element binding protein-1c (SREBP-1c), and adiponectin. Furthermore, the decrease of these transcriptional factors resulted in the repressed expression of several lipogenic genes including fatty acid binding protein (FABP4), fatty acid synthase (FAS), and lipoprotein lipase (LPL). In addition, SSA and SSD enhanced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC), and inhibited the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun-N-terminal kinase (JNK). These results suggest that SSA and SSD inhibit adipogenesis through the AMPK or mitogen-activated protein kinase (MAPK) pathways in the early stages of adipocyte differentiation. This is the first study on the anti-adipogenic effects of SSA and SSD, and further research in animals and humans is necessary to confirm the potential of saikosaponins as therapeutic agents for obesity.

show abstract

Kudinoside-D, a triterpenoid saponin derived from Ilex kudingcha suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes

Cited by 20 publications

References 29 publications

Melatonin reduces intramuscular fat deposition by promoting lipolysis and increasing mitochondrial function

Melatonin reduces intramuscular fat deposition by promoting lipolysis and increasing mitochondrial function

Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis

Saikosaponin A and D Inhibit Adipogenesis via the AMPK and MAPK Signaling Pathways in 3T3-L1 Adipocytes

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