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Salvianolic Acid B Improves Mitochondrial Function in 3T3-L1 Adipocytes Through a Pathway Involving PPAR? Coactivator-1? (PGC-1?).

ABSTRACT: Purpose: Mitochondrial dysfunction in adipose tissue has emerged as key to the development of obesity and diabetes. Salvianolic acid B (SalB) is a water-soluble ingredient derived from Salvia miltiorrhiza that has been shown to possess potential anti-obese and anti-diabetic activities. However, the cellular mechanism of SalB on mitochondrial function with respect to these metabolic disorders has not been elucidated. Therefore, we aim to investigate the effects of SalB on mitochondrial function in 3T3-L1 adipocytes and analyze the underlying molecular mechanism. Methods: The effects of SalB on adipocyte differentiation, glucose uptake, and glycerol release were evaluated in 3T3-L1 adipocytes. Differentiated adipocytes were treated with SalB (50 ?M) with or without PPAR? antagonist (GW9662, 20 ?M) for 48 h, and mitochondrial oxygen consumption rate (OCR) as well as extracellular acidification rate (ECAR) were assessed using an XF Extracellular Flux Analyzer. The mitochondrial distribution of adipocytes was assessed using Mito Tracker Green (MTG) and observed under a fluorescent microscope. In addition, the mRNA expression levels of peroxisome proliferators-activated receptor ?/? (PPAR?/?), CCAAT/enhancer binding protein? (C/EBP?), Nuclear respiratory factor 1/2 (NRF1/2), Uncoupling protein 2 (UCP2), and phosphofructokinase 2/fructose-2, 6-bisphosphatase 2 (PFKFB2) were detected by RT-PCR. Finally, changes in the protein levels of peroxisome proliferators-activated receptor ? coactivator-1? (PGC-1?) were determined by western blotting and immunofluorescence analysis. Results: Treatment with SalB increased glucose uptake and mitochondrial respiration, reduced glycerol release and promoted adipocyte differentiation by increasing mRNA expression of adipogenic transcription factors including PPAR?, C/EBP?, and PPAR?. Furthermore, SalB enhanced adipocytes mitochondrial content, mitochondrial respiration and glycolysis capacity, which had been attenuated by GW9662 treatment through the increased expression of PGC-1?. Conclusion: Our results provide novel insights into the role of PGC-1? and mitochondria as probable mediators of SalB activity in the regulation of adipocyte differentiation in 3T3-L1 adipocytes.

SUBMITTER: Pan Y

PROVIDER: S-EPMC6060424 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Salvianolic Acid B Improves Mitochondrial Function in 3T3-L1 Adipocytes Through a Pathway Involving PPARγ Coactivator-1α (PGC-1α).

Pan Yanyun Y Zhao Wenjing W Zhao Dandan D Wang Chaoyang C Yu Na N An Tian T Mo Fangfang F Liu Jiaxian J Miao Jianan J Lv Bohan B Gu Yujie Y Gao Sihua S Jiang Guangjian G

Frontiers in pharmacology 20180719

<b>Purpose:</b> Mitochondrial dysfunction in adipose tissue has emerged as key to the development of obesity and diabetes. Salvianolic acid B (SalB) is a water-soluble ingredient derived from <i>Salvia miltiorrhiza</i> that has been shown to possess potential anti-obese and anti-diabetic activities. However, the cellular mechanism of SalB on mitochondrial function with respect to these metabolic disorders has not been elucidated. Therefore, we aim to investigate the effects of SalB on mitochondr ...[more]

PMID: 30072891

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Project description:Gegen Qinlian Decoction (GQD), a well-documented traditional Chinese Medicine (TCM) formula, was reported with convincing anti-diabetic effects in clinical practice. However, the precise antidiabetic mechanism of GQD remains unknown. In this study, the anti-hyperglycemic and/or lipid lowering effects of GQD were demonstrated in high-fat diet with a low dose of streptozotocin induced diabetic Sprague-Dawley rats and insulin resistance (IR)-3T3-L1 adipocytes. GQD treatment increased expression and activity levels of both PPAR? and PPAR? in adipocytes, which transcriptionally affected an ensemble of glucose and lipid metabolic genes in vivo and in vitro. The results clearly indicated that GQD treatment intervened with multiple pathways controlled by concomitantly downstream effects of adipocytic PPAR? and PPAR?, to influence two opposite lipid pathways: fatty acid oxidation and lipid synthesis. Antagonist GW9662 decreased the mRNA expression of Ppar? and target genes Adpn and Glut4 whereas GW6471 decreased the mRNA expression of Ppar? and target genes Cpt-1?, Lpl, Mcad, Lcad, Acox1, etc. Nuclear location and activity experiments showed that more PPAR? and PPAR? shuttled into nuclear to increase its binding activities with target genes. GQD decreased the phosphorylation level of ERK1/2 and/or CDK5 to elevate PPAR? and PPAR? activities in IR-3T3-L1 adipocytes through post-translational modification. The increase in p-p38MAPK and SIRT1 under GQD treatment may be attributed to partially reduce PPAR? adipogenesis activity and/or activate PPAR? activity. Compared with the rosiglitazone-treated group, GQD elevated Cpt-1? expression, decreased diabetic biomarker Fabp4 expression, which produced an encouraging lipid profile with triglyceride decrease partially from combined effects on upregulated adipocytic PPAR? and PPAR? activities. These results suggested that GQD improved diabetes by intervening a diverse array of PPAR? and PPAR? upstream and downstream signaling transduction cascades, which jointly optimized the expression of target gene profiles to promote fatty acid oxidation and accelerate glucose uptake and utilization than PPAR? full agonist rosiglitazone without stimulating PPAR? activity. Thus, GQD showed anti-diabetic/or antihyperglycemic effects, partially through regulating adipocytic PPAR? and PPAR? signaling systems to maintaining balanced glucose and lipid metabolisms. This study provides a new insight into the anti-diabetic effect of GQD as a PPAR?/? dual agonist to accelerate the clinical use.

Dataset Information

Salvianolic Acid B Improves Mitochondrial Function in 3T3-L1 Adipocytes Through a Pathway Involving PPAR? Coactivator-1? (PGC-1?).

Publications

Salvianolic Acid B Improves Mitochondrial Function in 3T3-L1 Adipocytes Through a Pathway Involving PPARγ Coactivator-1α (PGC-1α).

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