Biochemical and Molecular Mechanisms of Olive Oil in Amelioration of Diabetes in Rats

Abstract

In modern lifestyle characterized by automation and decreased physical activity, obesity and obesity-associated syndromes have been a major public health concern. There is a widely known association between obesity and T2D. β-cell dysfunction and insulin resistance (IR) represent the two major pathological factors in developing T2D. As chronic overnutrition is the main driver of insulin resistance and streptozotocin is a known β-cell toxin, we used the HFD/STZ model to induce T2D in rats. We used a chronic high fat-feeding (12 weeks) that induced insulin resistance. Then, a low dose of STZ (30 mg/kg) was injected to trigger the diabetic condition. After validation of diabetes induction, olive oil and hydroxytyrosol treatment started and lasted for 8 weeks. A high-quality olive oil was used with a high polyphenolic content and total hydroxytyrosol of 191.9 mg/kg of the oil. To distinguish the beneficial effects of hydroxytyrosol alone, hydroxytyrosol was supplemented to another vegetable oil in a similar concentration as in olive oil. At the end of the experiment, we found that oral glucose tolerance was enhanced due to olive oil and hydroxytyrosol consumption. The biochemical and molecular basis of that effect was studied in the major insulin-sensitive tissues: the liver, the white adipose tissue, the skeletal muscles, and β-cells. We found that olive oil and hydroxytyrosol (in the used doses) differed slightly in ameliorating the HFD/STZ induced diabetes. Olive oil improved energy homeostasis and reduced IMCL by increasing thermogenesis. That was parallel to increasing the catalase enzyme activity in skeletal muscles. Catalase is an antioxidant enzyme that is expressed under control of PGC-1α, a transcription coactivator that enhances thermogenesis by upregulating uncoupling proteins expression. On the other hand, hydroxytyrosol restored adipose tissue insulin sensitivity and augmented adipocytes responsiveness to insulin stimulation. Furthermore, hydroxytyrosol protected β-cell mass and function. Finally, both olive oil and hydroxytyrosol enhanced adiponectin expression by alleviating adipose tissue ER stress and conveyed a general antioxidant environment that is associated with increased insulin sensitivity.