Molecular changes in hepatic metabolism in ZDSD rats–A new polygenic rodent model of obesity, metabolic syndrome, and diabetes

Lu Han, Stefanie Bittner, Dachuan Dong, Yuan Cortez, Alex Bittner, Jackie Chan, Meenakshi Umar, Wen Jun Shen, Richard G. Peterson, Fredric B. Kraemer, Salman Azhar

Research output: Contribution to journalArticle

Abstract

In recent years, the prevalence of obesity, metabolic syndrome and type 2 diabetes is increasing dramatically. They share pathophysiological mechanisms and often lead to cardiovascular diseases. The ZDSD rat was suggested as a new animal model to study diabetes and the metabolic syndrome. In the current study, we have further characterized metabolic and hepatic gene expression changes in ZDSD rats. Immuno-histochemical staining of insulin and glucagon on pancreas sections of ZDSD and control SD rats revealed that ZDSD rats have severe damage to their islet structures as early as 15 weeks of age. Animals were followed till they were 26 weeks old, where they exhibited obesity, hypertension, hyperglycemia, dyslipidemia, insulin resistance and diabetes. We found that gene expressions involved in glucose metabolism, lipid metabolism and amino acid metabolism were changed significantly in ZDSD rats. Elevated levels of ER stress markers correlated with the dysregulation of hepatic lipid metabolism in ZDSD rats. Key proteins participating in unfolded protein response pathways were also upregulated and likely contribute to the pathogenesis of dyslipidemia and insulin resistance. Based on its intact leptin system, its insulin deficiency, as well as its timeline of disease development without diet manipulation, this insulin resistant, dyslipidemic, hypertensive, and diabetic rat represents an additional, unique polygenic animal model that could be very useful to study human diabetes.

Original languageEnglish
Article number165688
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1866
Issue number5
DOIs
Publication statusPublished - 1 May 2020

    Fingerprint

Keywords

  • ER stress
  • Insulin resistance
  • Metabolic syndrome
  • Type 2 diabetes
  • ZDSD

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this