Combination of Capsaicin and Capsiate Induces Browning in 3T3-L1 White Adipocytes via Activation of the Peroxisome Proliferator-Activated Receptor γ/ß3-Adrenergic Receptor Signaling Pathways.

This study investigated the effects and molecular mechanism of a combination of capsaicin and capsiate on promoting lipid metabolism and inducing browning in 3T3-L1 white adipocytes. The combination significantly suppressed lipid accumulation in adipocytes ( p = 0.019) and robustly improved lipid metabolic profiles, including decreased triacylglycerol (0.6703 ± 0.0385 versus 0.2849 ± 0.0188 mmol/g of protein; p < 0.001), total cholesterol (0.1282 ± 0.0241 versus 0.0651 ± 0.0178 mmol/g of protein; p = 0.003), and low-density lipoprotein cholesterol (0.0021 ± 0.0017 versus 0.0005 ± 0.0002 mmol/g of protein; p = 0.024) and increased high-density lipoprotein cholesterol (0.0162 ± 0.0141 versus 0.1002 ± 0.0167 mmol/g of protein; p = 0.012). Furthermore, this combination markedly upgraded the protein levels of cluster of differentiation 36 ( p = 0.007) and adipose triglyceride lipase ( p = 0.013) and phosphorylation of hormone-sensitive lipase at Ser660, Ser565, and Ser563 ( p < 0.001, p = 0.027, and p = 0.002, respectively), indicating increases of fatty acid transport and lipolysis. The levels of lipid metabolism regulators, phosphorylation of adenosine-monophosphate-activated protein kinases α and ß ( p = 0.011, and p < 0.001, respectively), sirtuin 1 ( p = 0.004), and vanilloid transient receptor subtype I ( p = 0.014) were also increased by the combination. Moreover, the combination greatly activated the browning program in adipocytes, as demonstrated by increases in beige-specific gene and protein. Further research found that the protein levels of peroxisome proliferator-activated receptor γ (PPARγ; p = 0.001) and ß3-adrenergic receptor (ß3-AR; p = 0.026) were elevated by the combination, and most of the beige-specific markers were abolished by pretreatment of antagonists of PPARγ or ß3-AR. In conclusion, these results indicated that a combination of capsaicin and capsiate could induce browning in white adipocytes via activation of the PPARγ/ß3-AR signaling pathway, and this combination might be worth investigating as a potential cure for obesity.

Improvement of Lipid and Glucose Metabolism by Capsiate in Palmitic Acid-Treated HepG2 Cells via Activation of the AMPK/SIRT1 Signaling Pathway.

Capsiate, a nonpungent ingredient of CH-19 Sweet, exhibits anti-obesity effects on animals and humans. This study investigated the effects and molecular mechanism of capsiate on lipid and glucose metabolism in PA-treated HepG2 cells. Results showed that compared with the PA-alone group, 100 µM capsiate inhibited lipid accumulation, decreased TG (0.0562 ± 0.0142 vs 0.0381 ± 0.0055 mmol/g of protein; P = 0.024) and TC (0.1087 ± 0.0037 vs 0.0359 ± 0.0059 mmol/g of protein; P = 0.000) levels, and increased the HDL-C level (0.0189 ± 0.0067 vs 0.1050 ± 0.0106 mmol/g of protein; P = 0.000) and glycogen content (0.0065 ± 0.0007 vs 0.0146 ± 0.0008 mg/106 cells; P = 0.000) of PA-treated HepG2 cells; 100 µM capsiate also upregulated the level of CD36 ( P = 0.000), phosphorylation of ACC ( P = 0.034), and expression of CPT1 ( P = 0.013) in PA-treated HepG2 cells, leading to an enhancement of lipid metabolism. Meanwhile, 100 µM capsiate upregulated the levels of GLUT1, GLUT4, GK, and phosphorylation of GS ( P = 0.001, 0.029, 0.000, and 0.045, respectively) and downregulated the PEPCK level ( P = 0.001) to improve glucose metabolism in PA-treated HepG2 cells. Furthermore, the levels of phosphorylation of AMPK and expression of SIRT1 in HepG2 cells were increased by a 100 µM capsiate treatment ( P = 0.001 and 0.000, respectively), while the FGF21 level was decreased ( P = 0.003). Most of these effects were reversed by pretreatment with compound C, a selective AMPK inhibitor. Thus, capsiate might improve lipid and glucose metabolism in HepG2 cells by activating the AMPK/SIRT1 signaling pathway.