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Acupuncture is reported to be effective in treating obesity related illnesses, but its mechanism is still unclear. To investigate this mechanism we applied electro-acupuncture (EA) in a mouse model of obesity and used RNA-seq to identify molecular consequences. Deletion of the transcription factor STAT5 from neurons (Stat5NKO) led to obesity. Acupuncture, in turn, reduced body weight and the ratio of epididymal white adipose tissue (Epi-WAT) to body weight, and it also decreased plasma concentrations of glucose, triglyceride, and cholesterol. In addition, EA increased cold endurance of Stat5NKO obese mice. EA reversed altered gene expressions in the hypothalamus and Epi-WAT, especially in the hypothalamus in Stat5NKO obese mice. This study provides, for the first time, insight into genomic networks of obesity and their modulation by electro-acupuncture, which in turn reveals potential mechanisms that explain acupuncture-induced weight-loss.

BACKGROUND: Acupuncture exerts cardioprotective effects on several types of cardiac injuries, especially myocardial ischemia (MI), but the mechanisms have not yet been well elucidated. Angiogenesis mediated by VEGF gene expression and its modification through histone acetylation has been considered a target in treating myocardial ischemia. This study aims to exam whether modulation of angiogenesis through H3K9 acetylation regulation at VEGF gene is one possible cardioprotective mechanism of acupuncture. RESULTS: We generated rat MI models by ligating the left anterior descending coronary artery and applied electroacupuncture (EA) treatment at the Neiguan (PC6) acupoint. Our results showed that acupuncture reversed the S-T segment change, reduced Q-wave area, decreased CK, CK-MB, LDH levels, mitigated myocardial remodeling, and promoted microvessel formation in the MI heart. RNA-seq analysis showed that VEGF-induced angiogenesis signaling was involved in the modulation of EA. Western blot results verified that the protein expressions of VEGF, Ras, phospho-p44/42 MAPK, phospho-p38 MAPK, phospho-SAPK/JNK and Akt, were all elevated significantly by EA treatment in the MI heart. Furthermore, increased H3K9 acetylation was also observed according with the VEGF. ChIP assay confirmed that EA treatment could notably stimulate the recruitment of H3K9ace at the VEGF promoter. CONCLUSIONS: Our study demonstrates for the first time that acupuncture can effectively up-regulate VEGF expression through H3K9 acetylation modification directly at the VEGF promoter and hence activate VEGF-induced angiogenesis in rat MI models. We employed high throughput sequencing in this study and, for the first time, generated genome-wide gene expression profiles both in the rat MI model and in acupuncture treatment.