[Electroacupuncture improves glucose and lipid metabolism by regulating APN/AMPK/PPARα signaling of skeletal muscle in Zucker diabetic obese rats]

Abstract

Objective: To observe the effect of electroacupuncture (EA) on skeletal muscle adiponectin receptor (Adipor1) / adenylate activated protein kinase (AMPK) / peroxisome proliferator-activated receptor α (PPARα) signaling pathway and skeletal muscle morphology by the secretion of serum adiponectin in Zucker diabetic obese (ZDF) rats, so as to explore its mechanism underlying regulating glucose and lipid metabolism of type 2 diabetes mellitus (T2DM) and improving skeletal muscle insulin resistance (IR).

Methods: Twelve male ZDF rats and six Zucker thin (ZL) rats were selected. The rats were fed with Purina#5008 high-fat diet for four weeks to induce T2DM model after adaptive feeding with normal diet for one week. The ZDF rats were randomly divided into model group and EA group according to blood glucose level after modeling and 6 ZL rats were used as the blank control group. Rats in the EA group were treated with "Pishu" (BL20), EA stimulation of "Yishu" (EX-B3), "Zusanli" (ST36) and "Sanyinjiao" (SP6), once a day and 6 times a week for 4 weeks. Rats of the model and blank control groups were grabbed and fixed in the same way as EA group. Fasting blood glucose (FBG) was measured before and after EA intervention. Serum levels of insulin (INS), C-peptide (C-P), adiponectin (APN) were measured by radioimmunoassay, and those of free fatty acid (FFA), low-density lipoprotein (LDL), cholesterol (TC), triglyceride (TG) content determined by enzyme colorimetry and insulin resistance index (HOMA-IR) was calculated. The protein expression levels of AdipoR1, AMPK and PPARα proteins in the quadriceps femoris tissues were detected by Western blot and histopathological changes of quadriceps femoris muscle were observed by H.E. staining.

Results: Compared with the blank control group, the levels of FBG, serum INS, C-P, FFA, LDL, TC, TG and HOMA-IR in the model group were significantly increased (P<0.01, P<0.05), while the levels of serum APN and the expressions of AdipoR1, AMPK and PPARα proteins in the skeletal muscle were significantly decreased (P<0.01, P<0.05). Compared with the model group, the levels of FBG, serum INS, C-P, FFA, LDL, TC and HOMA-IR in the EA group were significantly decreased (P<0.01), and those of serum APN and expression levels of AdipoR1, AMPK and PPARα proteins in the skeletal muscle significantly increased (P<0.01), but the serum TG level had no remarkable change in the EA group (P>0.05). In addition, H.E. staining showed disordered arrangement of skeletal muscle cells, rupture and fuzziness of muscle fibers, enlargement of the space between muscular fibers and infiltration of small number of adipose cells which were relatively milder in the EA group.

Conclusion: EA can reduce blood glucose and lipid levels, and improve IR in ZDF rats, which may be related to its functions in up-regulating AdipoR1/AMPK/PPARα signaling and in promoting APN secretion.

Keywords: Adiponectin signaling pathway; Disorder of glucose and lipid metabolism; Electroacupuncture; Insulin resistance; Type 2 diabetes.