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oai:recercat.cat:2445/1351232025-12-05T09:23:49Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Cordoba-Chacon, Jose author Majumdar, Neena author List, Edward O. author Diaz, Alberto author Frank, Stuart J. author Manzano Cuesta, Anna author Bartrons Bach, Ramon author Puchowicz, Michelle author Kopchick, John J. author Kineman, Rhonda D. author 2019-06-14T14:00:57Z 2019-06-14T14:00:57Z 2015-09 2019-06-14T14:00:57Z 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. Glucocinasa Somatotropina Metabolisme Malalties del fetge Genètica RNA Ratolins (Animals de laboratori) Glucokinase Somatotropin Metabolism Liver diseases Genetics RNA Mice (Laboratory animals) Growth hormone inhibits hepatic de novo lipogenesis in adult mice