A Combination of Capsaicin and Capsiate Induces Browning in 3T3-L1 White Adipocytes via Activation of the PPARγ/ β3-AR 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 = 0.0190) and robustly improved lipid metabolic profiles, including the decreased TG (0.6703 ± 0.0385 vs 0.2849 ± 0.0188 mmol/g of protein; P ＜ 0.0010), TC (0.1282 ± 0.0241 vs 0.0651 ± 0.0178 mmol/g of protein; P = 0.0030) and LDL-C (0.0021 ± 0.0017 vs 0.0005 ± 0.0002 mmol/g of protein; P = 0.0240) and increased HDL-C (0.0162 ± 0.0141 vs 0.1002 ± 0.0167 mmol/g of protein; P = 0.0120). Furthermore, this combination markedly upgraded the protein levels of CD36 (P = 0.0070), ATGL (P = 0.0130) and phosphorylation of HSL at Ser660, 565 and 563 (P ＜ 0.0010, P = 0.0270 and 0.0020, respectively), indicating increases of fatty acid transport and lipolysis. The levels of lipid metabolism regulators, phosphorylation of AMPKα and β (P = 0.0110 and P ＜ 0.0010, respectively), SIRT1 (P = 0.0040) and TRPV1 (P = 0.0140) 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 PPARγ (P = 0.0010) and β3-AR (P = 0.0260) were elevated by the combination, and most of the beige specific markers were abolished by pretreatment of antagonists of PPARγ or β3-AR. In conclusion, these results indicated that a combination of capsaicin and capsiate could induce browning in white adipocytes via activation of the PPARγ/ β3-AR signaling pathway, and this combination might be worth investigating as a potential cure for obesity.