Open AccessThe acute effects of growth hormone in adipose tissue is associated with suppression of antilipolytic signals
Author(s) -
Høyer Katrine L.,
Høgild Morten L.,
List Edward O.,
Lee Kevin Y.,
Kissinger Emily,
Sharma Rita,
Erik Magnusson Nils,
Puri Vishwajeet,
Kopchick John J.,
Jørgensen Jens O. L.,
Jessen Niels
Publication year - 2020
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.14373
Subject(s) - lipolysis , endocrinology , downregulation and upregulation , medicine , adipose tissue , signal transduction , pten , insulin receptor , biology , gene expression , insulin , insulin resistance , gene , pi3k/akt/mtor pathway , microbiology and biotechnology , biochemistry
Aim Since GH stimulates lipolysis in vivo after a 2‐hr lag phase, we studied whether this involves GH signaling and gene expression in adipose tissue (AT). Methods Human subjects ( n = 9) each underwent intravenous exposure to GH versus saline with measurement of serum FFA, and GH signaling, gene array, and protein in AT biopsies after 30–120 min. Human data were corroborated in adipose‐specific GH receptor knockout (FaGHRKO) mice versus wild‐type mice. Expression of candidate genes identified in the array were investigated in 3T3‐L1 adipocytes. Results GH increased serum FFA and AT phosphorylation of STAT5b in human subjects. This was replicated in wild‐type mice, but not in FaGHRKO mice. The array identified 53 GH‐regulated genes, and Ingenuity Pathway analysis showed downregulation of PDE3b , an insulin‐dependent antilipolytic signal, upregulation of PTEN that inhibits insulin‐dependent antilipolysis, and downregulation of G0S2 and RASD1, both encoding antilipolytic proteins. This was confirmed in 3T3‐L1 adipocytes, except for PDE3B , including reciprocal effects of GH and insulin on mRNA expression of PTEN, RASD1 , and G0S2.Conclusion ( a) GH directly stimulates AT lipolysis in a GHR‐dependent manner, (b) this involves suppression of antilipolytic signals at the level of gene expression, (c) the underlying GH signaling pathways remain to be defined.