Poster Presentation ESA-SRB Conference 2015

Tamoxifen reduces hepatic VLDL production in women: a possible GH-mediated mechanism for the development of fatty liver  (#217)

Vita Birzniece 1 2 , Hugh Barrett 3 , Ken KY Ho 1 4
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. University, Penrith, NSW, Australia
  3. School of Medicine and Pharmacology, The University of Western Australia, Perth, WA, Australia
  4. Centres for Health Research, Princess Alexandra Hospital, Brisbane, Qld, Australia

Steatosis is a common complication of growth hormone (GH) deficiency. GH plays a vital role in lipid metabolism, stimulating hepatic fat oxidation and the synthesis of very-low-density lipoproteins (VLDL) for export of triglycerides (TGs). We previously reported that tamoxifen suppresses the secretion and hepatic action of GH1. We hypothesize that the GH-deficient state induced by tamoxifen, lowers the secretion of VLDL.

Objective: To investigate whether tamoxifen inhibits hepatic VLDL secretion.

Design: Eight healthy, normolipidemic women (BMI 23.7±1.2 kg/m2, age 64.4±2.2 years) were studied at baseline and after 2 weeks of tamoxifen (20 mg/d) treatment. We quantified apolipoprotein B (apoB), the structural protein of VLDL particles, by stable isotope 2H3-leucine turnover technique using steady state methodology. The enrichment of labelled leucine into VLDL-apoB was measured using gas chromatography mass spectroscopy. VLDL-apoB fractional catabolic rate (FCR) was determined using a multicompartment model. VLDL-apoB secretion was estimated as the product of FCR and VLDL-apoB concentration. Circulating levels of IGF-I, FFA, and TG were measured at baseline and following tamoxifen treatment.

Results: At baseline, mean VLDL-apoB concentration was 94±19.8 mg/L. VLDL-apoB FCR and secretion were 3.7±0.6 pools/d and 4.6±1.1 mg/kg/d, respectively. Tamoxifen significantly (p<0.05) lowered VLDL-apoB concentration and secretion by 27.6±7.8% and 30.7±9.8%, respectively. Tamoxifen also significantly lowered circulating IGF-I concentration (14.8±5.3%; p<0.05). There were no significant changes in plasma TG and FFA levels following tamoxifen treatment.

Summary: Tamoxifen significantly lowered VLDL-apoB concentration as a consequence of a lower production rate. Tamoxifen significantly reduced IGF-I, a hepatic marker of GH action.

Conclusion: The suppression of GH-IGF-I axis by tamoxifen is associated with lower rates of VLDL-apoB secretion. Diminished hepatic VLDL secretion may contribute to the development of fatty liver during tamoxifen therapy.

Supported by the Princess Alexandra Hospital Research Support Scheme and the NHMRC Australia.

  1. Birzniece et al., Paracrine regulation of growth hormone secretion by estrogen in women. JCEM 2010;95:3771-6