Growth hormone inhibits hepatic de novo lipogenesis in adult mice

Jose Cordoba-Chacon, Neena Majumdar, Edward O. List, Alberto Diaz-Ruiz, Stuart J. Frank, Anna Manzano, Ramon Bartrons, Michelle Puchowicz, John J. Kopchick, Rhonda D. Kineman

Research output: Contribution to journalArticle

26 Citations (Scopus)

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, hepatocytespecific, 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.

Original languageEnglish (US)
Pages (from-to)3093-3103
Number of pages11
JournalDiabetes
Volume64
Issue number9
DOIs
StatePublished - Sep 1 2015

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Lipogenesis
Growth Hormone
Liver
Somatotropin Receptors
Glucokinase
Sexual Maturation
Glycolysis
Fatty Liver
Lipid Metabolism
Rodentia
Insulin
Diet
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Cordoba-Chacon, J., Majumdar, N., List, E. O., Diaz-Ruiz, A., Frank, S. J., Manzano, A., ... Kineman, R. D. (2015). Growth hormone inhibits hepatic de novo lipogenesis in adult mice. Diabetes, 64(9), 3093-3103. https://doi.org/10.2337/db15-0370

Growth hormone inhibits hepatic de novo lipogenesis in adult mice. / Cordoba-Chacon, Jose; Majumdar, Neena; List, Edward O.; Diaz-Ruiz, Alberto; Frank, Stuart J.; Manzano, Anna; Bartrons, Ramon; Puchowicz, Michelle; Kopchick, John J.; Kineman, Rhonda D.

In: Diabetes, Vol. 64, No. 9, 01.09.2015, p. 3093-3103.

Research output: Contribution to journalArticle

Cordoba-Chacon, J, Majumdar, N, List, EO, Diaz-Ruiz, A, Frank, SJ, Manzano, A, Bartrons, R, Puchowicz, M, Kopchick, JJ & Kineman, RD 2015, 'Growth hormone inhibits hepatic de novo lipogenesis in adult mice', Diabetes, vol. 64, no. 9, pp. 3093-3103. https://doi.org/10.2337/db15-0370
Cordoba-Chacon J, Majumdar N, List EO, Diaz-Ruiz A, Frank SJ, Manzano A et al. Growth hormone inhibits hepatic de novo lipogenesis in adult mice. Diabetes. 2015 Sep 1;64(9):3093-3103. https://doi.org/10.2337/db15-0370
Cordoba-Chacon, Jose ; Majumdar, Neena ; List, Edward O. ; Diaz-Ruiz, Alberto ; Frank, Stuart J. ; Manzano, Anna ; Bartrons, Ramon ; Puchowicz, Michelle ; Kopchick, John J. ; Kineman, Rhonda D. / Growth hormone inhibits hepatic de novo lipogenesis in adult mice. In: Diabetes. 2015 ; Vol. 64, No. 9. pp. 3093-3103.
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