Activation of AMP-Activated Protein Kinase-Sirtuin 1 Pathway Contributes to Salvianolic Acid A-Induced Browning of White Adipose Tissue in High-Fat Diet Fed Male Mice

Abstract

Background: Salvianolic acid A (Sal A), a natural polyphenolic compound extracted from Radix Salvia miltiorrhiza (Danshen), exhibits exceptional pharmacological activities against cardiovascular diseases. While a few studies have reported anti-obesity properties of Sal A, the underlying mechanisms are largely unknown. Given the prevalence of obesity and promising potential of browning of white adipose tissue to combat obesity, recent research has focused on herbal ingredients that may promote browning and increase energy expenditure.Purpose: The present study was designed to investigate the protective antiobesity mechanisms of Sal A, in part through white adipose browning.Methods: Both high-fat diet (HFD)-induced obese (DIO) male mice model and fully differentiated C3H10T1/2 adipocytes from mouse embryo fibroblasts were employed in this study. Sal A (20 and 40 mg/kg) was administrated to DIO mice by intraperitoneal injection for 13-weeks. Molecular mechanisms mediating effects of Sal A were evaluated.Resluts: Sal A treatment significantly attenuated HFD-induced weight gain and lipid accumulation in epididymal fat pad. Uncoupling protein 1 (UCP-1), a specialized thermogenic protein and marker for white adipocyte browning, was significantly induced by Sal A treatment in both white adipose tissues and cultured adipocytes. Further mechanistic investigations revealed that Sal A robustly reversed HFD-decreased AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) expression in mice. Genetically silencing either AMPK or SIRT1 using siRNA abolished UCP-1 upregulation by Sal A. AMPK silencing significantly blocked Sal A-increased SIRT1 expression, while SIRT1 silencing did not affect Sal A-upregulated phosphorylated-AMPK. These findings indicate that AMPK was involved in Sal A-increased SIRT1.Conclusion: Sal A increases white adipose tissue browning in HFD-fed male mice and in cultured adipocytes. Thus, Sal is a potential natural therapeutic compound for treating and/or preventing obesity.

Chemical Profiles and Antiobesity Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract in High Fat Diet Fed Mice

“…Obesity is caused by the expansion of white adipose tissue and a decrease in brown adipose tissue. In a previous study by Lai et al, salvianolic acid A increased browning of white adipose tissue in high-fat diet-induced mice [46]. It is thought that components such as ononin or salvianolic acid may have affected the anti-obesity activity of the ALM16 in various ways.…”

Salvianolic acid A promotes mitochondrial biogenesis and mitochondrial function in 3T3-L1 adipocytes through regulation of the AMPK-PGC1α signalling pathway

“…PGC-1α is known to regulate the expression of NRF1, which further regulates the expression of TFAM [ 33 ]. After transcribed in the cytoplasm, TFAM is transported to mitochondria and acts as a key regulator of mitochondrial transcription and replication [ 34 , 35 ]. The PGC-1α-NRF1-TFAM network is closely related to the regulation of mitochondrial biogenesis in cells [ 8 , 9 , 33 , 34 ].…”

Effect of natural polyphenols in Chinese herbal medicine on obesity and diabetes: Interactions among gut microbiota, metabolism, and immunity

“…Browning of white adipose is crucial for metabolism based on reducing insulin resistance (IR) and increasing energy consumption. Salvianolic acid could promote adipocyte thermogenesis and energy expenditure via the activation of the AMPK-Sirtuin-1 pathway and upregulation of Uncoupling protein-1 (UCP-1) ( 104 ). Moreover, salvianolic acid B may play an anti-obesity role by adjusting the expression of mRNAs correlated with inflammatory response and energy metabolism of brown adipose tissue through regulating lncRNA-Hsd11b1 and lncRNA-Vmp1 ( 105 ).…”