Salvianolic acid B induces browning in 3T3-L1 white adipocytes via activation of β3-AR and ERK signaling pathways

Pham, Huong Giang; Dang, Trang Thi Huyen; Yun, Jong Won

doi:10.1016/j.jff.2021.104475

Cited by 7 publications

(4 citation statements)

References 43 publications

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“…The current study also revealed that the ECH treatment downregulated the core adipogenic transcription factors (C/EBPα and PPARγ), suggesting its inhibiting role in adipogenesis. The effect of ECH in our current study is consistent with the role of various phytochemicals in the literature that inhibits adipogenesis and lipogenesis [ 9 , 26 , 27 ].…”

Section: Discussionsupporting

confidence: 91%

“…A growing body of evidence indicates that phytochemicals mediate thermogenesis via the stimulation of the β3-AR [ 9 , 26 , 27 ]. These molecules target various pathways that are intricately linked to the process of adipogenesis, lipogenesis, lipolysis, and the fat oxidation process, all of which provide a fertile environment for high energy expenditure in the metabolic machinery [ 11 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

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Echinacoside Induces UCP1- and ATP-Dependent Thermogenesis in Beige Adipocytes via the Activation of Dopaminergic Receptors

Haddish

Yun

2023

J. Microbiol. Biotechnol.

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Echinacoside (ECH) is a naturally occurring phenylethanoid glycoside, isolated from Echinacea angustifolia , and this study aimed to analyze its effect on thermogenesis and its interaction with dopaminergic receptors 1 and 5 (DRD1 and DRD5) in 3T3-L1 white adipocytes and mice models. We employed RT-PCR, immunoblot, immunofluorescence, a staining method, and an assay kit to determine its impact. ECH showed a substantial increase in browning signals in vitro and a decrease in adipogenic signals in vivo. Additionally, analysis of the iWAT showed that the key genes involved in beiging, mitochondrial biogenesis, and ATP-dependent thermogenesis were upregulated while adipogenesis and lipogenesis genes were downregulated. OXPHOS complexes, Ca 2+ signaling proteins as well as intracellular Ca 2+ levels were also upregulated in 3T3-L1 adipocytes following ECH treatment. This was collectively explained by mechanistic studies which showed that ECH mediated the beiging process via the DRD1/5-cAMP-PKA and subsequent downstream molecules, whereas it co-mediated the α1-AR-signaling thermogenesis via the DRD1/5/SERCA2b/RyR2/CKmt pathway in 3T3-L1 adipocytes. Animal experiments revealed that there was a 12.28% reduction in body weight gain after the ECH treatment for six weeks. The effects of ECH treatment on adipose tissue can offer more insights into the treatment of obesity and metabolic syndrome.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Echinacoside Induces UCP1- and ATP-Dependent Thermogenesis in Beige Adipocytes via the Activation of Dopaminergic Receptors

Haddish

Yun

2023

J. Microbiol. Biotechnol.

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“…Both β3-AR and ERK pathways have been shown to be involved in the induction of brown adipocytes from white adipocytes in independent ways (11). ERK1/2 is a member of the large MAPK family and includes a family of serine/threonine kinases with cellular and molecular functions (12). In humans and rats, two ERK isoforms (ERK1 and ERK2) are expressed and play role in many cellular processes, including proliferation, inflammation, as well as metabolism (13).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Swimming Training with Cinnamon Consumption on β3-AR and ERK2 Gene Expression in the Visceral Adipose Tissue of Diabetic Rats

2022

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Background: β3-AR is an important factor involved in the activation of ERK protein signaling cascade, which can positively contribute to the regulation of adipose tissue metabolism and its conversion into brown adipose tissue. Diabetes mellitus can lead to dysfunction of these factors. Objectives: The current study aimed to investigate the effect of swimming training combined with cinnamon consumption on β3-AR and ERK2 gene expression in the visceral adipose tissue from diabetic rats. Methods: In this experimental-fundamental study, 35 male Wistar rats (mean weight: 200 ± 20 g) were selected and randomly assigned into four groups after the induction of diabetes by streptozotocin. These groups included: (1) healthy control, (2) control, (3) swimming, (4) cinnamon, and (5) swimming cinnamon (n = 7 in each group). The training groups were put through a five-days-a-week workout for four weeks according to the training protocol. Gene expression levels were measured by in vitro real-time PCR. The collected data were analyzed using one-way ANOVA and Tukey’s post hoc test. Results: The expression levels of β3-AR and ERK2 protein genes in the visceral adipose tissue of diabetic rats (P = 0.0001) were significantly affected by swimming training and cinnamon consumption. Conclusions: It was shown that cinnamon supplementation may have increased β3-AR levels, which was more effective than training, while training had a greater effect on ERK2 levels and increased them. Therefore, it was concluded that cinnamon consumption combined with training may have greatly contributed to the conversion of white adipose into brown adipose tissues.

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“…Moreover, Sal B also found to have effects in lipid metabolism by reducing fasting blood glucose, total cholesterol, triglycerides (TGs), low-density lipoprotein cholesterol, and increasing high-density lipoprotein levels in mice [22]. However, other studies demonstrated that Sal B could promote adipocyte differentiation in 3T3-L1 cells by increasing PPAR-γ, PPAR-α, and C/EBP-α mRNA expression levels and improve fat graft survival [23,24].…”

Section: Introductionmentioning

confidence: 99%

Anti-adipogenic Effect and Mechanism in 3T3-L1 Preadipocyte Differentiation by Salvianolic Acid B

Kwon

Jang

2022

Keimyung Med J

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Salvianolic acid B (Sal B) is one of the most active hydrophilic compounds extracted from Salvia miltiorrhiza root. Previous in vitro and in vivo studies demonstrate the ability of Sal B to modulate adipocyte differentiation. However, the lipid-modulating effect and mechanism of Sal B in adipocytes remain controversial. Here we investigated the regulatory effect and mode of action of Sal B on lipid accumulation in 3T3-L1 preadipocyte differentiation. Lipid droplet (LD) accumulation and triglyceride (TG) content during 3T3-L1 preadipocyte differentiation were measured by Oil Red O staining and AdipoRed assay. The growth inhibition during 3T3-L1 preadipocyte differentiation was measured by cell count analysis. Western blotting and real-time qPCR analysis were utilized to determine the protein and mRNA expression in the preadipocyte differentiation. Notably, in 3T3-L1 preadipocyte differentiation, treatment with Sal B at 100 M led to a marked decrease in LD accumulation and TG content without influencing cell growth. Sal B treatment (100 M) further reduced the expression and phosphorylation levels of adipogenic transcription factors, including CCAAT/enhancer-binding protein- (C/EBP-), peroxisome proliferator-activated receptor-gamma (PPAR)-, and signal transducer and activator of transcription (STAT)-3/5. Treatment with Sal B (100 M) also reduced the expression and phosphorylation levels of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), two lipogenic enzymes and perilipin A, an LD-binding and stabilizing protein. These results collectively demonstrate that Sal B at 100 M strongly inhibits lipid accumulation in 3T3-L1 preadipocyte differentiation, mediated through regulation of the expression and phosphorylation levels of C/EBP-, PPAR-, STAT-3/5, FAS, ACC, and perilipin.

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Salvianolic acid B induces browning in 3T3-L1 white adipocytes via activation of β3-AR and ERK signaling pathways

Cited by 7 publications

References 43 publications

Echinacoside Induces UCP1- and ATP-Dependent Thermogenesis in Beige Adipocytes via the Activation of Dopaminergic Receptors

Echinacoside Induces UCP1- and ATP-Dependent Thermogenesis in Beige Adipocytes via the Activation of Dopaminergic Receptors

The Effect of Swimming Training with Cinnamon Consumption on β3-AR and ERK2 Gene Expression in the Visceral Adipose Tissue of Diabetic Rats

Anti-adipogenic Effect and Mechanism in 3T3-L1 Preadipocyte Differentiation by Salvianolic Acid B

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