Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2014) 34 P224 | DOI: 10.1530/endoabs.34.P224

SFEBES2014 Poster Presentations Obesity, diabetes, metabolism and cardiovascular (80 abstracts)

DLK1/PREF1 prevents hepatosteatosis by elevating pituitary GH secretion

Marika Charalambous 1, , Simao daRocha 1, & Anne Ferguson-Smith 1


1University of Cambridge, Cambridge, UK; 2Queen Mary University of London, London, UK; 3Institute Curie, Paris, France.


GH deficiency is clinically associated with non-alcoholic fatty liver disease. Here we describe a new in vivo model of pituitary GH modulation resulting in protection from hepatosteatosis, by over-expression of delta-like homologue 1 (Dlk1/Pref1) from endogenous control elements. This resulted in improved glucose tolerance with no primary defect in adipose tissue expansion, even under extreme metabolic stress. Rather, Dlk1 overexpression caused pituitary IGF1 resistance and hence a defect in feedback regulation of GH. Circulating GH was elevated and accompanied by several physiological sequelae culminating in a switch in whole body fuel metabolism to favour fatty acid utilisation. Elevated serum DLK1 is observed in physiological states of high FA utilisation such as during pregnancy and before weaning. We propose that the normal function of DLK1 is to shift the metabolic mode of the organism toward peripheral FA oxidation and away from lipid storage, thus mediating important physiological adaptations associated with early life.

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