Electroacupuncture ameliorates hepatic defects in a rat model of polycystic ovary syndrome induced by letrozole and a high-fat diet

Acupunct Med. 2024 Apr;42(2):87-99. doi: 10.1177/09645284231207863. Epub 2023 Dec 4.

Abstract

Background: This study was designed to evaluate the effects of low-frequency electroacupuncture (EA) on glucose and lipid disturbances in a rat model of polycystic ovary syndrome (PCOS) characterized by insulin resistance (IR) and hepatic steatosis.

Methods: The PCOS rat model was induced by continuous administration of letrozole (LET) combined with a high-fat diet (HFD). Female Sprague-Dawley rats were divided into the following four groups: control, control + EA, LET + HFD and LET + HFD + EA. EA was administered five or six times a week with a maximum of 20 treatment sessions. Body weight, estrous cyclicity, hormonal status, glucose and insulin tolerance, lipid profiles, liver inflammation factors, liver morphology and changes in the phosphatidylinositol 3-kinase (PI3-K)/Akt (protein kinase B) pathway were evaluated.

Results: The rat model presented anovulatory cycles, increased body weight, elevated testosterone, abnormal glucose and lipid metabolism, IR, liver inflammation, hepatic steatosis and dysregulation of the insulin-mediated PI3-K/Akt signaling axis. EA reduced fasting blood glucose, fasting insulin, area under the curve for glucose, homeostasis model assessment of IR indices, triglycerides and free fatty acids, and alleviated hepatic steatosis. Furthermore, low-frequency EA downregulated mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6, upregulated mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α, increased protein expression of phosphorylated (p)-Akt (Ser473), p-glycogen synthase kinase (GSK) 3β (Ser9) and glucose transporter 4 (GLUT4), increased the ratio of p-GSK3β to GSK3β and downregulated protein expression of GSK3β.

Conclusion: An obese PCOS rat model with IR and hepatic steatosis was successfully established by the combination of LET and HFD. EA improved dysfunctional glucose and lipid metabolism in this PCOS-IR rat model, and the molecular mechanism appeared to involve regulation of the expression of key molecules of the PI3-K/Akt insulin signaling pathway in the liver.

Keywords: electroacupuncture; glucose and lipid disturbances; hepatic steatosis; insulin resistance; polycystic ovary syndrome.

MeSH terms

  • Animals
  • Body Weight
  • Diet, High-Fat / adverse effects
  • Electroacupuncture*
  • Female
  • Glucose / metabolism
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Inflammation / metabolism
  • Insulin / metabolism
  • Insulin Resistance* / physiology
  • Letrozole / metabolism
  • Liver / metabolism
  • Phosphatidylinositol 3-Kinase / metabolism
  • Polycystic Ovary Syndrome* / metabolism
  • Polycystic Ovary Syndrome* / therapy
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Triglycerides

Substances

  • Proto-Oncogene Proteins c-akt
  • Letrozole
  • Glycogen Synthase Kinase 3 beta
  • Insulin
  • Glucose
  • Phosphatidylinositol 3-Kinase
  • Triglycerides
  • RNA, Messenger