Short-term westernized (HFFD) diet fed in adolescent rats: Effect on glucose homeostasis, hippocampal insulin signaling, apoptosis and related cognitive and recognition memory function

Abstract

Excessive consumption of high-fat fructose diet (HFFD) is associated with the development of systemic insulin resistance (InsRes) and further progression into type-2 diabetes (T2DM). InsRes induced hippocampal insulin signaling has serious consequence on hampered sensorimotor, cognitive performance and long term potentiation accompained to neuronal cell death in hippocampus. However, short-term HFFD/Streptozotocin (STZ) mediated hippocampal InsRes and related neurobehavioral alterations in adoloscents have not been reported. Therefore, we investigated a one-week HFFD model to augment the state of InsRes along with a single sub-diabetogenic dose of STZ (45 mg/kg i.p) to produce a hampered hippocampal insulin signaling associated with frank hyperglycemia and other biochemical and neurobehavioral alterations in young rats. To achieve this, male wistar rats of age (8–10 weeks) and weight 80–120 g were divided into two main groups: (1) fed with commercial standard normal fat diet (NFD: 6.5% kcal fat) and (2) fed an in-house prepared high-fat diet [HFFD: 58% kcal fat] and 20% high-fructose corn syrup in the distilled water. Our results showed an increase in calorie intake, water intake, body weight and blood glucose levels. Further, an increase in fasting serum insulin and Homeostasis Model Assessment-index (HOMA-I) and oral glucose tolerance test (OGTT) was observed. Whereas, we observed a decrease in hippocampal insulin signaling and translocation of glucose transporter type 4 (GLUT4) to neuronal membrane. Further, HFFD/STZ mediated oxidative stress, lipid peroxidation (LPO), decreased antioxidant levels, Brain-derived neurotrophic factor (BDNF) levels and further activation of increase caspase-3 was observed. These battery of events indicate biochemical alterations in hippocampus resulting in cognition and memory deficit.