Electroacupuncture intervention promotes browning of white adipose tissue by regulating LKB1/AMPK pathway in obese mice

To observe the effect of electroacupuncture (EA) on hypothalamic liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) signaling pathway, sympathetic nerve activity and browning of white adipose tissue (WAT) in obese mice, so as to explore the possible central mechanisms of EA in improving obesity.

C57BL/6J male mice were divided into normal group (n=8) and high fat diet group (n=30) randomly, and fed by normal diet and high fat diet for 8 weeks, respectively. In the high fat diet group, mice with body weight over 20% heavier than that of the normal group were considered as obese mice. The obese mice were divided into model and EA groups (n=8 in each group). Mice in the EA group were treated with EA (2 Hz/15 Hz, 1 mA, 3 mm needling depth) at "Zusanli" (ST36) and "Tianshu" (ST25) for 30 min, 5 times a week for 4 weeks. The mice's body weight and length were measured for calculating the Lee's index. The contents of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and noradrenaline (NE) were detected by ELISA. The weight of abdominal white adipose tissue was weighed, and the morphological changes of abdominal adipose tissue were observed by HE staining. The mRNA and protein expression levels of LKB1 and AMPK in hypothalamus, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), uncoupling protein-1 (UCP1), peroxisome proliferator-activated receptor γ (PPAR-γ) and β3-adrenergic receptor (β3-AR) in abdominal white adipose tissue were detected by real-time fluorescence quantitative PCR and Western blot, respectively.

Compared with the normal group, the body weight, Lee's index, serum contents of TC, TG and LDL-C, abdominal WAT mass, hypothalamus LKB1, AMPK mRNA and protein expression were increased (P<0.01), while serum HDL-C and NE contents, mRNA and protein expression of β3-AR, PGC-1α, UCP1 and PPAR-γ in adipose tissue were decreased (P<0.01) in the model group. The diameter of adipocytes in abdominal WAT was significantly increased, and the number of cells per unit area was decreased in the model group. Following EA intervention, the body weight, Lee's index, serum contents of TC, TG and LDL-C, abdominal WAT mass, hypothalamus LKB1, AMPK mRNA and protein expression were decreased (P<0.01), while the serum HDL-C and NE contents, mRNA and protein expression of β3-AR, PGC-1α, UCP1 and PPAR-γ were increased (P<0.01). The diameter of adipocytes in abdominal WAT was decreased and the number of cells per unit area was increased in the EA group.

EA can reduce the body weight and Lee's index in obese mice, regulate blood lipids, and reduce the weight of abdominal WAT, which may be closely related to its effect in regulating the hypothalamic LKB1/AMPK signaling pathway, activating the adipose tissue sympathetic nerve activity, and promoting the browning of WAT.