Eletroacupuncture improves lipid metabolic disorder by regulating hepatic AMPK/p38 MAPK/RRARγ signaling in rats with high-fat diet-induced insulin resistance

Abstract

To observe the effect of eletroacupuncture (EA) intervention on lipid metabolism and expression of AMP-activated kinase (AMPK), p38 mitogen-activated protein kinase (p38 MAPK) and peroxisome proliferator-activated receptor γ (PPARγ) protein in the liver in rats with insulin resistance (IR), so as to reveal its mechanisms underlying improvement of IR. Forty male SD rats were randomly divided into blank control, model, medication, and EA groups (n＝8 in each). The IR model was established by feeding the rats with high-fat diet for 12 weeks. After successful establishment of model, the rats in the blank control group and model group were fixed in the self-made rat bag without receiving any treatment. The rats in the medication group were treated by gavage of pioglitazone (10 mL/kg). EA (2 Hz /100 Hz, 1 mA) was applied to bilateral "Fenglong"(ST40) and "Sanyinjiao"(SP6) for 20 min, once a day, for continuous 14 days for rats in the EA group. The ultrastructure of the liver tissue was observed by transmission electron microscope (TEM). Blood samples were taken from the abdominal aorta for detecting serum C-peptide (C-P), adiponectin (ADP), leptin (LEP) and resistin (RES) contents using enzyme linked immunosorbent assay (ELISA). The expression levels of AMPK, p38 MAPK and PPARγ proteins in the liver tissue were detected by Western blot. After modeling, the contents of serum C-P, LEP and RES, and the expression of liver p38 MAPK protein were significantly up-regulated (P<0.01, P<0.05), and the content of ADP and expression of AMPK and PPARγ significantly down-regulated in the model group compared with the blank control group (P<0.01). The increased contents of C-P, LEP and RES, and p38 MAPK protein expression and the decreased serum ADP and hepatic AMPK and PPARγ expression levels were completely reversed in both the EA and medication groups relevant to the model group (P<0.01, P<0.05). No significant differences were found between the EA and medication groups in up-regulating the levels of ADP, AMPK and PPARγ and in down-regulating the levels of C-P, LEP, RES and p38 MAPK(P>0.05). Outcomes of TEM showed that morphological structure of liver mitochondria was damaged, including a large number of lipid droplets, being blur in appearance, rupture of partial membrane, dissapearance of partial mitochondrial crests with vacuolus-like appearance and decrease of rough endoplasmic reticulum in the model group, which was relatively milder in both EA and medication groups. EA intervention is able to improve the disorder of lipid metabolism of IR rats, which may be associated with its effects in lowering the activity of fatty acid synthesis-related enzymes and regulating AMPK/p38 MAPK/PPARγ signaling to improve IR in the liver tissue.