Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
Estrogen prevents increased hepatic aquaporin-9 expression and glycerol uptake during starvation. / Lebeck, Janne; Gena, Patrizia; O'Neill, Heidi; Skowronski, Mariusz Tomasz; Lund, Sten; Calamita, Giuseppe; Prætorius, Jeppe.
In: American Journal of Physiology: Gastrointestinal and Liver Physiology, 2011.Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
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TY - JOUR
T1 - Estrogen prevents increased hepatic aquaporin-9 expression and glycerol uptake during starvation
AU - Lebeck, Janne
AU - Gena, Patrizia
AU - O'Neill, Heidi
AU - Skowronski, Mariusz Tomasz
AU - Lund, Sten
AU - Calamita, Giuseppe
AU - Prætorius, Jeppe
PY - 2011
Y1 - 2011
N2 - In starvation, glycerol is released from adipose tissue and serves as an important precursor for hepatic gluconeogenesis. By unknown gender-specific mechanisms, women suppress the endogenous glucose production better than men and respond to metabolic stress with higher plasma glycerol levels. Hepatic glycerol uptake is facilitated by aquaporin-9 (AQP9), a broad-selectivity neutral solute channel, and represents an insulin-regulated step in supplying gluconeogenesis with glycerol. In the current study, hepatic AQP9 abundance was increased 2.6-fold in starved male rats as assessed by immunoblotting and immunohistochemistry. By contrast, starvation had no significant effect on hepatic AQP9 expression in female rats. Coordinately, plasma glycerol levels remained unchanged upon starvation in male rats whereas it was increased in female rats. The different responses to starvation were paralleled by higher glycerol permeability in basolateral hepatocyte membranes from starved male rats as compared to starved females. Ovariectomy led to a starvation-response pattern identical to that observed in male rats with increased hepatic AQP9 expression and unchanged plasma glycerol levels. In cultured hepatocytes, 17β-estradiol and the selective estrogen receptor α agonist, propyl pyrazole triol, caused a decrease in AQP9 expression. Our results support that a gender specific regulation of the hepatic glycerol channel AQP9 during starvation contributes to the higher plasma glycerol levels observed in women during fasting and possibly results in a lower cytosolic availability of glycerol. Furthermore, the sexual dimorphism in the hepatic handling of glycerol during starvation might be explained by 17β-estradiol preventing the starvation-induced increase in hepatic AQP9 abundance.
AB - In starvation, glycerol is released from adipose tissue and serves as an important precursor for hepatic gluconeogenesis. By unknown gender-specific mechanisms, women suppress the endogenous glucose production better than men and respond to metabolic stress with higher plasma glycerol levels. Hepatic glycerol uptake is facilitated by aquaporin-9 (AQP9), a broad-selectivity neutral solute channel, and represents an insulin-regulated step in supplying gluconeogenesis with glycerol. In the current study, hepatic AQP9 abundance was increased 2.6-fold in starved male rats as assessed by immunoblotting and immunohistochemistry. By contrast, starvation had no significant effect on hepatic AQP9 expression in female rats. Coordinately, plasma glycerol levels remained unchanged upon starvation in male rats whereas it was increased in female rats. The different responses to starvation were paralleled by higher glycerol permeability in basolateral hepatocyte membranes from starved male rats as compared to starved females. Ovariectomy led to a starvation-response pattern identical to that observed in male rats with increased hepatic AQP9 expression and unchanged plasma glycerol levels. In cultured hepatocytes, 17β-estradiol and the selective estrogen receptor α agonist, propyl pyrazole triol, caused a decrease in AQP9 expression. Our results support that a gender specific regulation of the hepatic glycerol channel AQP9 during starvation contributes to the higher plasma glycerol levels observed in women during fasting and possibly results in a lower cytosolic availability of glycerol. Furthermore, the sexual dimorphism in the hepatic handling of glycerol during starvation might be explained by 17β-estradiol preventing the starvation-induced increase in hepatic AQP9 abundance.
U2 - 10.1152/ajpgi.00437.2011
DO - 10.1152/ajpgi.00437.2011
M3 - Journal article
C2 - 22114114
JO - American Journal of Physiology: Gastrointestinal and Liver Physiology
JF - American Journal of Physiology: Gastrointestinal and Liver Physiology
SN - 0193-1857
ER -