BAUMGARTNER Clemens

Effects of Growth Hormone on Hepatic Lipid Metabolism

Background: Non-alcoholic fatty liver disease (NAFLD) defines an increase in hepatic lipid content (HCL) and has become more and more prevalent over the past years. The amount of HCL is regulated by a balanced fatty acid flux depending on mechanisms including fatty acid oxidation, de-novo lipogenesis (DNL), and hepatic lipid export by secretion of VLDL1 particles. Recent studies suggest growth hormone (GH) excess a promotor of HCL decrease. However, the exact antisteatotic effects of GH remain to be elucidated, which might lay the foundation for new therapeutic targets in the treatment of NAFLD.

Aims: To investigate the influence of GH on hepatic lipid metabolism, we aim to i) provide an in-depth characterization of hepatic lipid metabolism in vivo in humans, before ii) identifying the impact of GH on hepatic lipid metabolism, and iii) characterizing antisteatotic effects in patients with acromegaly.

Methods: We will assess hepatic ATP turnover, VLDL1 secretion and DNL by using in-vivo examination techniques in 20 healthy volunteers and 10 acromegalic patients. Healthy volunteers will be examined by using a crossover balanced within-subject study design, investigating lipid metabolism before and after daily administration of Somatropin or Pegvisomant for one week. Acromegalic patients will be examined in the state of active acromegaly, as well as 6 and 12 months after initiation of treatment. Of each subject, HCL and ATP turnover will be examined by 1H/31-P MRS. The rate of VLDL1 secretion will be measured by using an established intralipid infusion protocol. Measurement of DNL will be provided by using novel deuterated water techniques.

Methods and Skills: 

Grandient ultracentrifugation; Elisa; MR spectroscopy