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Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice.

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Title: Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice.
Author(s): Cordoba-Chacon, J.; Majumdar, N.; List, EO; Diaz-Ruiz, A.; Frank, SJ; Manzano, A.; Bartrons, R.; Puchowicz, M.; Kopchick, JJ; Kineman, RD
Abstract: Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have low growth hormone (GH) production and/or hepatic GH resistance. GH replacement can resolve the fatty liver condition in diet-induced obese rodents and in GH-deficient patients. However, it remains to be determined whether this inhibitory action of GH is due to direct regulation of hepatic lipid metabolism. Therefore, an adult-onset, hepatocyte-specific, GH receptor (GHR) knockdown (aLivGHRkd) mouse was developed to model hepatic GH resistance in humans that may occur after sexual maturation. Just 7 days after aLivGHRkd, hepatic de novo lipogenesis (DNL) was increased in male and female chow-fed mice, compared with GHR-intact littermate controls. However, hepatosteatosis developed only in male and ovariectomized female aLivGHRkd mice. The increase in DNL observed in aLivGHRkd mice was not associated with hyperactivation of the pathway by which insulin is classically considered to regulate DNL. However, glucokinase mRNA and protein levels as well as fructose-2,6-bisphosphate levels were increased in aLivGHRkd mice, suggesting that enhanced glycolysis drives DNL in the GH-resistant liver. These results demonstrate that hepatic GH actions normally serve to inhibit DNL, where loss of this inhibitory signal may explain, in part, the inappropriate increase in hepatic DNL observed in NAFLD patients.
Issue Date: 2015-09
Publisher: American Diabetes Association
Citation Info: Cordoba-Chacon, J., Majumdar, N., List, E. O., Diaz-Ruiz, A., Frank, S. J., Manzano, A., Bartrons, R., Puchowicz, M., Kopchick, J. J. and Kineman, R. D. Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice. Diabetes. 2015. 64(9): 3093-3103. DOI: 10.2337/db15-0370.
Type: Article
Description: This is the author’s version of a work that was accepted for publication in Diabete. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cordoba-Chacon, J., Majumdar, N., List, E. O., Diaz-Ruiz, A., Frank, S. J., Manzano, A., Bartrons, R., Puchowicz, M., Kopchick, J. J. and Kineman, R. D. Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice. Diabetes. 2015. 64(9): 3093-3103. DOI: 10.2337/db15-0370.
URI: http://hdl.handle.net/10027/19877
ISSN: 0012-1797
Sponsor: Supported by: I01 BX001114/BX/BLRD VA/United States
Date Available in INDIGO: 2015-11-09
 

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