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Publication
Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice.
Authors Cordoba-Chacon J, Majumdar N, List EO, Diaz-Ruiz A, Frank SJ, Manzano A,
Bartrons R, Puchowicz M, Kopchick JJ, Kineman RD
Submitted By Submitted Externally on 11/3/2015
Status Published
Journal Diabetes
Year 2015
Date Published 9/1/2015
Volume : Pages 64 : 3093 - 103
PubMed Reference 26015548
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.




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