Niels Jessen

Growth hormone acts along PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes

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DOI

  • Vishva M Sharma
  • ,
  • Esben Thyssen Vestergaard
  • Niels Jessen
  • Peter Kolind-Thomsen
  • ,
  • Birgitte Nellemann
  • ,
  • Thomas S Nielsen
  • ,
  • Mikkel Holm Vendelbo
  • Niels Møller
  • Rita Sharma
  • ,
  • Kevin Y Lee, Ohio State University, Columbus Cancer Council, Columbus, Ohio, United States of America.
  • ,
  • John J Kopchick, Edison Biotechnology Institute; Department of Biomedical Sciences, College of Osteopathic Medicine; Molecular and Cellular Biology Program, Ohio University, United States.
  • ,
  • Jens Otto Lunde Jørgensen
  • Vishwajeet Puri, puri@ohio.edu, United States.

The lipolytic effects of GH have been known for half a century and play an important physiological role for substrate metabolism during fasting. In addition, sustained GH-induced lipolysis is causally linked to insulin resistance. However, the underlying molecular mechanisms remain elusive. In the present study, we obtained experimental data in human subjects and used human adipose-derived stromal vascular cells (hADSCs) as a model system to elucidate GH-triggered molecular signaling that stimulates adipose tissue lipolysis and insulin resistance in human adipocytes. We discovered that GH downregulates the expression of fat specific protein (FSP27), a negative regulator of lipolysis, by impairing the transcriptional ability of the master transcriptional regulator, peroxisome proliferator-activated receptor gamma (PPARγ) via MEK/ERK activation. Ultimately, GH treatment promotes phosphorylation of PPARγ at Ser273 and causes its translocation from nucleus to the cytosol. Surprisingly, FSP27 overexpression inhibited PPARγ Ser273 phosphorylation and promoted its nuclear retention. GH antagonist treatment had similar effects. Our study identifies a novel signaling mechanism by which GH transcriptionally induce lipolysis via MEK/ERK pathway that acts along PPARγ-FSP27 in human adipose tissue.

OriginalsprogEngelsk
TidsskriftA J P: Endocrinology and Metabolism (Online)
Vol/bind316
Nummer1
Sider (fra-til)E34-E42
Antal sider8
ISSN1522-1555
DOI
StatusUdgivet - 1 jan. 2019

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