Insulin deficiency: A possible link between obesity and cognitive function.

Background: Epidemiological studies proposed a linear connection between developing dementia including Alzheimer's disease (AD) and obesity. Adiposity, insulin resistance and dementia indicated probable mechanistic links in this process. Indeed, it has been known that optimum insulin action in the brain plays critical role in cognitive function; whereas, insulin resistance in obese individuals finally leads to insulin deficiency in central nervous system (CNS) and down regulation of the efficiency of insulin uptake from periphery into CSF. In the current study, we aimed to assess correlation between increased body weight and insulin resistance with CSF to serum ratio of insulin and to evaluate the correlation between CSF to serum ratio of insulin with cognitive function in high fat diet induced obese rats.
Methods and Material: Twelve male Wister rats were randomly divided into two groups receiving Diet 1 (D1, 10% fat) and Diet 2 (D2, 59% fat) for 16 weeks. Weight was recorded weekly to assure body weight gain. Morris Water Maze (MWM) task was designed to assess spatial learning memory function. Finally, blood samples were collected for determining fasting serum glucose using enzymatic spectrophotometric method, insulin levels by ELISA kit and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Fasting Cerebrospinal Fluid (CSF) insulin was also measured by ELISA kit.
Result: D1 and D 2 groups both experienced weight gain but weight gain in D2 group were significantly higher. A significant correlation between CSF to serum ratio of insulin with weight (r=0.882, p=0.001) and HOMA-IR index (r=0.798, p=0.002) was reported. Moreover, the present study indicated significant correlations between CSF to serum ratio of insulin and escape latency time in first (r=0.631, p=0.028), second (r=0.716, p=0.009) and third (r=0.609, p=0.036) day of MWM test and probe time of MWM test (r=0.762, p=0.004).
Conclusion: Increased body weight induced by high fat diet and insulin resistance in rats led to down regulation of CSF to serum ratio of insulin in the current research. Brain insulin deficiency may be responsible for possible decline of cognitive function in obesity. More researches are needed to better clarify the underlying mechanisms and also to confirm the similar findings in human studies.
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