Electroacupuncture prevents white adipose tissue inflammation through modulation of hypoxia-inducible factors-1α-dependent pathway in obese mice

BACKGROUND: Electroacupuncture (EA) shows anti-inflammation and several pleiotropic effects that interact with metabolic pathways. In the present study we tested the hypothesis that EA prevents inflammatory response and weight gain in obese mice through modulation of hypoxia-inducible factors-1α (HIF1-α)-dependent pathways in white adipose tissues. METHODS: Mice were divided in 4 groups: Non-obese, ob/ob, ob/ob submitted to 3 treatments, ob/ob submitted to 7 treatments. Low-frequency EA (2 Hz) was applied at the Zusanli (ST36) acupoint 10 min three times weekly for one or two consecutive weeks in male ob/ob mice. At 22 weeks of age, plasma lipid, glucose, other metabolites and relevant markers were measured by standard assays. Adipose tissue was assessed with immunohistochemical staining. Adipose tissue extracts were also analyzed with quantitative real-time polymerase chain reaction (Q-PCR) and Western blotting. RESULTS: EA treatment is associated with decreased adipose tissue inflammation, and markedly decreased fat mass and adipocyte size in ob/ob mice. In obese mice, The protein levels of HIF-α were increased, EA shown a marked trend in inhibiting the hypoxic response in adipose tissue. The expression level of hypoxia-related genes (vascular endothelial growth factor A, VEGFA; glucose transporter type 1, Slc2al; glutathione peroxidase 1, GPX1) and inflammation-related genes (TNF-α, IL-6, MCP-1) expression were also reduced in adipose tissue after EA treatment. EA treatment decreased the macrophage recruitment and infiltration (F4/80), and in addition we found that decrease in NF-κB and increase in IkBα were both correlated to reduction in inflammatory processes in adipose tissue. This phenomenon was paralleled by the decrease in the levels of inflammatory cytokines, such as TNF-α, IL-6 and IL-1β in obese mice. CONCLUSIONS: We conclude that EA prevents weight gain through modulation of HIF-1α-dependent pathways and inflammatory response in obese adipose tissues.