Journal of Krishna Institute of Medical Sciences University (Jan 2021)
Effect of Fenofibrate on Hippocampal Insulin Resistance and Cognitive Function in a Rat Model of Type 2 Diabetes Mellitus
Abstract
Background: Hippocampal insulin resistance elicits decline in cognitive function and increased risk of neurodegeneration. Subsequently, Fenofibrate (FEN) has been used in metabolic disorders to treat hypercholesterolemia, hypertriglyceridemia and Insulin Resistance (IR), and may play a protective role against hippocampal insulin resistance in type 2 diabetic rats. Aim and Objectives: To study the effect of FEN on hippocampal insulin resistance and cognitive function in a rat model of type 2 diabetes mellitus. Material and Methods: Twenty male Wistar rats with an average weight of 200 ± 10 grams were randomly divided into four groups (n = 5/group). Induction of IR in subsets of the experimental rats was done by concurrent administration of High Fat Diet (HFD) and Streptozotocin (STZ) in a sub-set of the experimental rats. A dose of intraperitoneal injection of STZ-30 mg/kg was administered to the subjects for five consecutive days, while they were allowed to feed freely on high-fat diet for 90 days. The rats that received post-induction treatment were given 100 mg/kg FEN administered via intra-gastric gavage for 14 consecutive days. At the end of the experiment, an open-field test was conducted after which the rats were sacrificed and measurement of fasting plasma glucose and insulin as indices for insulin sensitivity, evaluation of enzyme activity and histological studies were carried out. Results: There was significant increase in the indices of IR, elevated anxiety level, reduced G6PD activity, elevated G6Pase activity, with numerous vacuolization in the pyramidal layer of hippocampal tissue in the HFD+STZ group compared to the control. However, there were significantly lowered indices of insulin resistance, increased G6PD activity, decreased G6Pase and reduced extent of vacuolization in the group that received post-induction FEN relative to untreated group. Conclusion: PPARá agonist activity of FEN plays a neuroprotective role on the hippocampal structure through different mechanisms of increasing insulin sensitivity, reducing anxiety, regulating metabolic enzyme activities and reducing features of neurodegenerationin HFD- and STZ-induced type 2 diabetic rats.
