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The acute effects of growth hormone in adipose tissue is associated with suppression of antilipolytic signals.

ABSTRACT: 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.

SUBMITTER: Hoyer KL

PROVIDER: S-EPMC7029434 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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The acute effects of growth hormone in adipose tissue is associated with suppression of antilipolytic signals.

Høyer Katrine L KL Høgild Morten L ML List Edward O EO Lee Kevin Y KY Kissinger Emily E Sharma Rita R Erik Magnusson Nils N Puri Vishwajeet V Kopchick John J JJ Jørgensen Jens O L JOL Jessen Niels N

Physiological reports 20200201 3

<h4>Aim</h4>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).<h4>Methods</h4>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 gene ...[more]

PMID: 32073221

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Project description:Growth hormone (GH) supplementation therapy to adults with GH deficiency has beneficial effects on adipose tissue lipid metabolism, improving thus adipocyte functional morphology and insulin sensitivity. However, molecular nature of these effects remains unclear. We therefore tested the hypothesis that lipid-mobilizing adipokine zinc-?2-glycoprotein is causally linked to GH effects on adipose tissue lipid metabolism. Seventeen patients with severe GH deficiency examined before and after the 5-year GH replacement therapy were compared with age-, gender- and BMI-matched healthy controls. Euglycemic hyperinsulinemic clamp was used to assess whole-body and adipose tissue-specific insulin sensitivity. Glucose tolerance was determined by oGTT, visceral and subcutaneous abdominal adiposity by MRI, adipocyte size morphometrically after collagenase digestion, lipid accumulation and release was studied in differentiated human primary adipocytes in association with GH treatment and zinc-?2-glycoprotein gene silencing. Five-year GH replacement therapy improved glucose tolerance, adipose tissue insulin sensitivity and reduced adipocyte size without affecting adiposity and whole-body insulin sensitivity. Adipose tissue zinc-?2-glycoprotein expression was positively associated with whole-body and adipose tissue insulin sensitivity and negatively with adipocyte size. GH treatment to adipocytes in vitro increased zinc-?2-glycoprotein expression (>50%) and was paralleled by enhanced lipolysis and decreased triglyceride accumulation (>35%). Moreover, GH treatment improved antilipolytic action of insulin in cultured adipocytes. Most importantly, silencing zinc-?2-glycoprotein eliminated all of the GH effects on adipocyte lipid metabolism. Effects of 5-year GH supplementation therapy on adipose tissue lipid metabolism and insulin sensitivity are associated with zinc-?2-glycoprotein. Presence of this adipokine is required for the GH action on adipocyte lipid metabolism in vitro.

Dataset Information

The acute effects of growth hormone in adipose tissue is associated with suppression of antilipolytic signals.

Publications

The acute effects of growth hormone in adipose tissue is associated with suppression of antilipolytic signals.

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