Growth hormone promotes in-vivo hepatic triglyceride export in humans

Clemens Baumgartner; Matthaeus Metz; Lorenz Pfleger; Anna Tosin; Marianna Beghini; Hannes Beiglboeck; Paul Fellinger; Franziska Schnait; Greisa Vila; Anton Luger; Alexandra Kautzky-Willer; Angelika Freudenthaler; Sabina Baumgartner-Parzer; Herbert Stangl; Martin Krssak; Thomas Scherer; Michael Krebs; Peter Wolf

doi:10.1530/endoabs.99.OC12.3

OC12.3

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Endocrine Abstracts (2024) 99 OC12.3 | DOI: 10.1530/endoabs.99.OC12.3

ECE2024 Oral Communications Oral Communications 12: Diabetes, Obesity, Metabolism and Nutrition | Part II (6 abstracts)

Growth hormone promotes in-vivo hepatic triglyceride export in humans

Clemens Baumgartner ^1,2 , Matthaeus Metz ¹ , Lorenz Pfleger ¹ , Anna Tosin ¹ , Marianna Beghini ¹ , Hannes Beiglboeck ¹ , Paul Fellinger ¹ , Franziska Schnait ¹ , Greisa Vila ¹ , Anton Luger ¹ , Alexandra Kautzky-Willer ¹ , Angelika Freudenthaler ¹ , Sabina Baumgartner-Parzer ¹ , Herbert Stangl ³ , Martin Krssak ^1,4 , Thomas Scherer ¹ , Michael Krebs ¹ & Peter Wolf ¹

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¹Medical University of Vienna, Department of Endocrinology and Metabolism, Wien, Austria; ²Medical University of Vienna, Clinical Department of Nephrology and Dialysis, Wien, Austria; ³Medical University of Vienna, Institute of Medical Chemistry, Center for Pathobiochemistry and Genetics, Wien, Austria; ⁴Medical University of Vienna, High-Field MR Centre, Department of Biomedical Imaging and Image-Guided Therapy, Wien, Austria

Overview: Non-alcoholic fatty liver disease (NAFLD) is defined as a chronic increase in intrahepatic lipids (IHL). A surplus of IHL can be compensated through increased lipid export via very-low density lipoprotein (VLDL) particles. Growth hormone (GH) is known to reduce visceral and ectopic fat. However, the main pathways responsible for the in-vivo decrease of IHL under the influence of GH are yet to be determined.

Methods: We assessed hepatic lipid metabolism of 10 healthy, male volunteers (26±5 years; BMI=23±3 kg/m²) before and after one week of daily subcutaneous treatment with either 2 mg Genotropin® or the GH-antagonist Somavert® (20 mg/day, loading dose of 40 mg at the first day) in a single blinded, crossover balanced study design. After a washout period of ≥6 weeks (116±67 days), the study protocol was repeated with the respective other drug. Experiments comprised IHL measurement withH-magnetic resonance spectroscopy, fasting blood analysis and the quantification of VLDL1-triglyceride (VLDL-TG) secretion via an intralipid infusion protocol.

Results: After GH treatment, IHL slightly increased in 8 of 10 cases, but drastically decreased in two participants with IHL >10% at baseline (11.2 and 12%, respectively). With respect to other participants (n=8), the increase in IHL reached statistical significance (0.9±0.5% vs 1.6±0.9, P=0.005). Secretion of VLDL1-TG was available for nine subjects and showed an overall increase of 26.1% (590.5±282.3 mg/h vs 738.8±424.9 mg/h, P=0.035). After Somavert®, IHL also tended to increase in all ten participants compared to baseline (no significance), whereby no trends were observed regarding VLDL1-TG secretion. Marked and divergent changes in serum concentrations of IGF-1, insulin, and c-peptide during both conditions indicated a sufficient impact of individual treatment.

Conclusion: Our findings demonstrate a GH mediated increase in hepatic VLDL1-TG secretion. The promoted efflux of hepatic lipids may in the long term even be responsible for an overall decrease in IHL. We further report increases in IHL after both short-term GH excess and suppression. However, a slight increase in IHL due to GH-mediated lipolysis in white adipose tissue appears reasonable. We conclude that promoted VLDL1-TG secretion in response to short term GH therapy may be beneficial for hepatic lipid turnover and might lay the foundation of novel therapeutic strategies against NAFLD.