Role of Agouti-related peptide producing neurons, but not Steroidogenic Factor 1 neurons, in mediating leptin's anti-diabetic actions in mice
Leptin is an adipokine that interacts with the brain to control energy balance and regulates circulating glucose concentrations. However, the direct mechanism or the specific neurons that carry out these actions have not been elucidated. Recent studies have shown that Pro-opiomelanocortin neurons in the Arcuate Nucleus play a pivotal role in leptin's anti-diabetic action; however, other leptin receptor expressing neurons in the brain may also be involved. The data points to other hypothalamic neurons such as Agouti-related peptide and Steroidogenic Factor 1 producting neurons. In this study the Cre-Lox system was used to add leptin receptors back in to Agouti-related peptide or Steroidogenic Factor 1 (dbAgRP-LepRb or dbSF1-LepRb, respectively) neurons in the leptin receptor deficient (Lepr^db/db) mice. The body weights and blood glucose levels of these mice were evaluated from 3 weeks to 11 weeks of age. The body weights of mice that expressed leptin receptor b in Agouti-related peptide neurons showed no statically significant difference compared to Lepr^db/db mice (p-value > 0.05). The body weights of mice that re-expressed leptin receptor b in Steroidogenic Factor 1 neurons also had similar body weights to the Lepr^db/db mice. However, the Lepr^db/db mice that expressed leptin receptors in Agouti-related peptide neurons had a marked decrease in blood glucose levels via ANOVA analysis (p-value less than 0.001). This was not seen in the dbSF1-LepRb mice. The results indicate that leptin's signaling through Agouti-related peptide neurons were sufficient at decrease blood glucose levels in Lepr^db/db mice. We concluded that Agouti-related peptide neurons may play a critical role in leptin's anti-diabetic actions in mice.
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