Abstract
BackgroundElectroacupuncture (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.MethodsMice 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.ResultsEA 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.ConclusionsWe conclude that EA prevents weight gain through modulation of HIF-1α-dependent pathways and inflammatory response in obese adipose tissues.
Highlights
Electroacupuncture (EA) shows anti-inflammation and several pleiotropic effects that interact with metabolic pathways
Macrophages infiltrate and orchestrate inflammatory responses via molecules such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1), all of which have been implicated in pathological changes in adipose tissue (AT) physiology [8, 9]
In order to further identify possible mechanisms of EA for obesity related complication we investigated in the present study whether the hypoxia—induced inflammationin adipose tissue could be reversed by EA treatment in obese mice
Summary
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. Both experimental and clinical current data suggest that acupuncture exerts beneficial effects on the mechanisms of obesity and obesity-related insulin resistance [10,11,12]. We have shown that EA treatment improves the inflammation in the adipose tissue by reducing the expression and release of cytokines in rat [14] This result indicates that EA may have potentiality in the treatment of obesity and its complication. The purpose of this study was to determine the effects of EA on ST36 acupoint on adipose tissue mRNA expression of hypoxia and macrophage markers in ob/ob mice over 1 or 2 weeks treatment and to determine the relationships between these markers and adipose tissue inflammatory gene expression
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