Background: Brain insulin receptor is considered an important regulatory factor
for appetite regulation, white fat mass metabolism, and hepatic glucose output. Disruption
of neuronal insulin action leads to obesity, metabolic syndrome and neurodegenerative
Objective: The aim of the present study was to find out the effect of exenatide, a GLP-1
analog, on the hypothalamic insulin receptor (IR) gene expression in high fat diet (HFD)
obesity rat model.
Method: Rats were fed on HFD for 16 weeks and received exenatide (10μg/kg/d, SC) for
one month. The body weight difference, fasting blood glucose, fasting insulin levels,
HOMA index, lipid profile, oxidative stress markers and serum TNF-α were measured.
Additionally, hypothalamic IR gene expression was analyzed using real time polymerase
Results: HFD rats showed significant body weight gain, hyperglycemia, hyperinsulinemia,
insulin resistance, dyslipidemia, and increase in the oxidative stress and TNFα together
with down-regulation of IR gene expression in the hypothalamus. Exenatide significantly
reduced the body weight, fasting blood glucose and insulin levels, insulin resistance,
dyslipidemia, the oxidative stress and TNF-α serum level. Also, exenatide caused significant
up-regulation of hypothalamic IR gene expression.
Conclusion: In conclusion, exenatide may exert hypothalamic insulin-sensitizing effect
along with its antiinflammatory and antioxidant effects in HFD obese rats.