Acta Veterinaria et Zootechnica Sinica ›› 2024, Vol. 55 ›› Issue (11): 5247-5258.doi: 10.11843/j.issn.0366-6964.2024.11.040

• Basic Veterinary Medicine • Previous Articles     Next Articles

Thiazolidinedione Inhibits Chicken Growth via Adiponectin-mediated AMPK Signaling Pathway

Yao TANG(), Tao WANG, Mengqing XUE, Wenyu ZHANG, Mei SHI, Xianzhong WANG, Jiaojiao ZHANG*()   

  1. College of Veterinary Medicine, Southwest University, Chongqing 400715, China
  • Received:2024-01-11 Online:2024-11-23 Published:2024-11-30
  • Contact: Jiaojiao ZHANG E-mail:1264142767@qq.com;zhangjjff@126.com

Abstract:

Thiazolidinedione (TZD) is an oral anti-diabetic drug for the treatment of insulin resistance. Abuse or improper use of TZD has adverse effects on animal and human health. This study explores effects of TZD on the growth and metabolism of chicks and underlying mechanisms of this process. Eighty chicks at the age of 6-day-old were divided into a control group (20 females, 20 males) and an experimental group (20 females, 20 males). Chicks in the control group were administered without TZD, chicks in the experimental group were daily administrated with 25 mg·(kg·d)-1 TZD by gavage for 14 days, and the growth of chicks was measured. The biochemical kits were used to detect the levels of adenosine triphosphate (ATP) and adiponectin, the concentrations of growth and metabolism-related hormones, and the function of mitochondria. The mRNA and protein expressions of genes which are associated with cell metabolism and proliferation were detected by RT-PCR and western blotting. Results showed that TZD treatment significantly decreased the average daily gain of chicks (P < 0.05). Serum ATP, insulin (INS), growth hormone (GH), and insulin-like growth factor 1 (IGF1) levels were reduced in TZD-treated group (P < 0.05), while adiponectin and insulin-like growth factor binding protein 2 levels was improved (P < 0.05). TZD also decreased ATP levels and mitochondrial enzyme activities in the liver, kidney and muscle of chicks. Moreover, mRNA and protein expressions of adiponectin and its receptors, AMP-activated protein kinase α2 (AMPKα2), p21 and p27 were enhanced in TZD-treated chicks (P < 0.05), whereas mRNA and protein expressions of INS and its receptor, IGF1 and its receptor, phosphatidylinositol-3-kinase (PI3K), AKT, mammalian target of rapamycin (mTOR), Cyclin-dependent kinase 2 (CDK2) and Cyclin E1 were inhibited (P < 0.05). The growth metabolism-related hormones and mitochondrial function in TZD-treated chicks were down-regulated by the adiponectin-mediated AMPK signaling pathway, which inhibited its downstream PI3K/AKT/mTOR, and further led to increased expressions of p21/p27 and decreased expressions of CDK2/Cyclin E1, this inhibiting the cell proliferation in growth and metabolic tissues of chicks. Our findings suggest that TZD has an adverse effect on chicken growth through regulating the adiponectin-mediated AMPK signaling pathway, this provides a certain theoretical basis for avoiding the abuse or improper use of TZD in clinical practice and animal production.

Key words: thiazolidinedione, growth metabolism, adiponectin, AMPK

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