Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 P269

ICEECE2012 Poster Presentations Cardiovascular Endocrinology and Lipid Metabolism (74 abstracts)

Testosterone replacement therapy inhibits key enzymes of fatty acid synthesis in mouse liver

J. Brooke 1, , D. Kelly 1 , S. Akhtar 1 , V. Muraleedharan 1, & T. Jones 1,

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1University of Sheffield, Sheffield, UK; 2Barnsley Hospital, Barnsley, UK.


Fatty liver (Hepatic Steatosis) is common in men with type 2 diabetes mellitus (T2DM). Furthermore there is a high prevalence of testosterone deficiency (up to 40%) in this population. Testosterone replacement therapy (TRT) has been shown to reduce elevated serum liver transaminase levels in hypogonadal men. The testicular feminised (Tfm) mouse exhibits a non-functional androgen receptor (AR) and low circulating testosterone levels. We have previously shown that a high-fat diet promotes hepatic steatosis in the Tfm mouse and TRT attenuates these changes. Our objectives were to determine the effect of testosterone on the key regulatory enzymes of fatty acid synthesis in mouse liver.

Tfm mice were fed a high-fat diet for 28 weeks and received either physiological testosterone replacement (Tfm+t, n=12) or placebo (Tfm+p, n=12) and were compared to wild-type (XY, n=12) littermates. Relative concentrations of mRNA were analysed by qPCR for expression of Fatty Acid Synthase (FAS) and Acetyl-CoA Carboxylase (ACC). Protein expression was analysed by western blotting.

There was an increase in mRNA expression of FAS (Relative fold increase 11.4±4.93, P=0.06) and ACC (2.5±0.64, P=0.05) in the Tfm mice compared to wild-type littermates. In the Tfm+t group, mRNA expression was significantly reduced for FAS, but ACC showed a non-significant decrease relative to the Tfm+p group. Western blotting densitometry confirmed that the Tfm+p group had significantly increased levels of ACC (3.47±0.27 vs 1.22±0.22, P<0.001) and FAS (2.43±0.37 vs 0.88±0.22, P=0.002) protein expression compared to XY wild-type. In the Tfm+t group ACC protein decreased to a level comparable to the XY wild-type (1.53±0.21 vs 1.22±0.22, P=0.30) as did FAS (0.88±0.22 vs 0.89±0.17, P=0.97).

This is the first evidence to show that a testosterone deficient state is associated with increased FAS and ACC expression which promotes hepatic steatosis, and TRT suppresses both enzymes. This beneficial action of testosterone is independent of the androgen receptor.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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