Janne Lebeck

Hepatic AQP9 expression in male rats is reduced in response to PPARα agonist treatment

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  • Janne Lebeck
  • Muhammad Umar Cheema, Denmark
  • Mariusz Tomasz Skowronski, University of Warmia and Mazury., Denmark
  • Søren Nielsen, Aarhus University, Denmark
  • Jeppe Praetorius

The peroxisome proliferator receptor α (PPARα) is a key regulator of the hepatic response to fasting with effects on both lipid and carbohydrate metabolism. A role in hepatic glycerol metabolism has also been found, however the results are somewhat contradictive. AQP9 is a pore-forming transmembrane protein that facilitates hepatic uptake of glycerol. Its expression is inversely regulated by insulin in male rodents, with increased expression during fasting. Previous results indicate that PPARα plays a crucial role in the induction of AQP9 mRNA during fasting. In the present study, we use PPARα-agonists to explore the effect of PPARα-activation on hepatic AQP9 expression and on the abundance of enzymes involved glycerol metabolism using both in vivo and in vitro systems. In male rats with free access to food, treatment with the PPARα-agonist WY 14643 (3 mg/kg/day) caused a 50% reduction in hepatic AQP9 abundance with the effect being restricted to AQP9 expressed in periportal hepatocytes. The pharmacological activation of PPARα had no effect on the abundance of GlyK, whereas it caused an increased expression of hepatic GPD1, GPAT1 and L-FABP protein. In WIF-B9 and HepG2 hepatocytes, both WY 14643 and another PPARα-agonist GW 7647 both reduced the abundance of AQP9 protein. In conclusion, pharmacological PPARα-activation results in a marked reduction in the abundance of AQP9 in periportal hepatocytes. Together with the effect on the enzymatic apparatus for glycerol metabolism, our results suggest that PPARα-activation in the fed state directs glycerol into glycerolipid synthesis rather than into de novo synthesis of glucose.

Original languageEnglish
JournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Pages (from-to)ajpgi.00407.2013
Publication statusPublished - 4 Dec 2014

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