Role of leptin receptor in the dorsal vagal complex in the inhibition of food intake in obese mice by electroacupuncture at “Zusanli” (ST36)

To observe the role of leptin receptor (LepR) in the dorsal vagal complex (DVC) in electroacupuncture (EA)-mediated regulation of food intake, so as to explore its central mechanism underlying improvement of metabolic disorders.

Ten C57BLKS/JGpt mice were randomly selected as the normal group, and the remaining mice were fed with high-fat diet (HFD) to establish a obesity model. Successfully modeled mice were randomly divided into the HFD group and EA group, with 10 mice in each group. The EA group received EA stimulation (2 mA, 2 Hz/15 Hz) at bilateral “Zusanli” (ST36) for 20 min, once daily, 6 times per week, for 5 weeks. The body weight, food intake, liver tissue wet weight, inguinal white adipose tissue (iWAT) weight, epididymal white adipose tissue (eWAT) and brown adipose tissue (BAT) weight, and blood glucose levels were measured. The serum insulin and leptin contents were measured using ELISA. Immunofluorescence staining was used to detect the co-expression of LepR and proto-oncogene c-Fos protein (c-Fos), the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the nucleus tractus solitarii (NTS) and dorsal motor nucleus of the vagus nerve (DMV), and the co-expression of choline acetyltransferase (ChAT) and c-Fos in DMV.

Compared with the normal group, the HFD group showed a significant increase in the body weight, liver and adipose (iWAT, eWAT and BAT) wet weight, serum insulin and leptin contents, fasting blood glucose level, and glucose tolerance area under the curve (AUC, P<0.01), the number of LepR and c-Fos co-expression neurons in the DMV and NTS, p-STAT3 positive and ChAT and c-Fos co-expression neurons in the DMV were remarkably decreased (P<0.05, P<0.01). In comparison with the HFD group, the body weight, food intake, liver and adipose wet weight, serum leptin content, fasting blood glucose, and glucose tolerance AUC were significantly decreased in the EA group (P<0.01), while the number of LepR and c-Fos co-expression neurons in the DMV and NTS, p-STAT3 positive and ChAT and c-Fos co-expression neurons in the DMV were notably increased in the EA group (P<0.05, P<0.01). No significant differences were observed in the random blood glucose content and p-STAT3 positive expression in the NTS among the three groups and in the serum level of insulin after EA.

EA at ST36 can inhibit food intake and reduce body weight in obesity mice, which may be associated with restoration of LepR-ralated signaling in the DVC and improvement of cholinergic vagal efferent neuronal activity in the DMV.