Effects of short-term prednisolone treatment on indices of lipolysis and lipase signaling in abdominal adipose tissue in healthy humans

Nilani Ramshanker; Niels Jessen; Thomas Schmidt Voss; Steen Bønløkke Pedersen; Jens Otto Lunde Jørgensen; Thomas Svava Nielsen; Jan Frystyk; Niels Møller

doi:10.1016/j.metabol.2019.06.013

Effects of short-term prednisolone treatment on indices of lipolysis and lipase signaling in abdominal adipose tissue in healthy humans

Nilani Ramshanker, Niels Jessen, Thomas Schmidt Voss, Steen Bønløkke Pedersen, Jens Otto Lunde Jørgensen, Thomas Svava Nielsen, Jan Frystyk, Niels Møller

4 Citations (Scopus)

Abstract

BACKGROUND: Glucocorticoid (GC) excess increases lipolysis, circulating free fatty acid concentrations and lipid oxidation rates in humans. In vitro and animal studies have shown that GCs increase adipocyte ATGL and HSL mRNA contents and HSL phosphorylations, but the effects of GC on in vivo lipase signaling in humans are uncertain. Our study was designed to test how GC administration affects ATGL and HSL related signals in human adipose tissue.

MATERIAL AND METHODS: Nine healthy young men underwent 5 days administration of 37.5 mg prednisolone/d in a randomized, double-blinded, placebo-controlled crossover design. At the end of each 5 d period the subjects were studied after an overnight fast for 6.5 h including a basal period and a 2½ h hyperinsulinemic euglycemic clamp. Adipose tissue biopsies were sampled from the abdominal subcutaneous adipose tissue at the end of the basal period and the clamp.

RESULTS: GC treatment increased serum FFA concentrations and comparative gene identification-58 (CGI-58) mRNA - an ATGL activator - and decreased G0/G1 switch 2 gene (G0S2) mRNA - an ATGL inhibitor - in adipose tissue biopsies. In addition, pro-lipolytic ser563 HSL phosphorylations and protein kinase A (PKA) phosphorylation of PLIN1 (Perilipin-1) increased. The transcripts of ANGPTL4 (Angiopoietin-like 4) mRNA - a regulator of circulating triglycerides - were elevated by GC; as were CIDE (Cell-death Inducing DNA fragmentation factor-α-like Effector)-A and CIDE-C mRNA transcripts indicative of concurrent stimulation of lipolysis and lipogenesis. Finally GCs reduced insulin receptor phosphorylation, and Akt protein levels.

CONCLUSIONS: High dose GC administration to humans leads to pro-lipolytic alterations of CGI-58, G0S2 and ANGPTL4 mRNA transcripts, increases PKA signaling to lipolysis and inhibits the insulin signal in adipose tissue. The increased CIDE-A and CIDE-C mRNA levels suggest concomitant stimulation of lipolysis and lipid storage.

Original language	English
Journal	Metabolism: Clinical and Experimental
Volume	99
Pages (from-to)	1-10
ISSN	0026-0495
DOIs	https://doi.org/10.1016/j.metabol.2019.06.013
Publication status	Published - Oct 2019

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10.1016/j.metabol.2019.06.013

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@article{d24dd57402ba447fb4287e6ba81104af,

title = "Effects of short-term prednisolone treatment on indices of lipolysis and lipase signaling in abdominal adipose tissue in healthy humans",

abstract = "BACKGROUND: Glucocorticoid (GC) excess increases lipolysis, circulating free fatty acid concentrations and lipid oxidation rates in humans. In vitro and animal studies have shown that GCs increase adipocyte ATGL and HSL mRNA contents and HSL phosphorylations, but the effects of GC on in vivo lipase signaling in humans are uncertain. Our study was designed to test how GC administration affects ATGL and HSL related signals in human adipose tissue.MATERIAL AND METHODS: Nine healthy young men underwent 5 days administration of 37.5 mg prednisolone/d in a randomized, double-blinded, placebo-controlled crossover design. At the end of each 5 d period the subjects were studied after an overnight fast for 6.5 h including a basal period and a 2½ h hyperinsulinemic euglycemic clamp. Adipose tissue biopsies were sampled from the abdominal subcutaneous adipose tissue at the end of the basal period and the clamp.RESULTS: GC treatment increased serum FFA concentrations and comparative gene identification-58 (CGI-58) mRNA - an ATGL activator - and decreased G0/G1 switch 2 gene (G0S2) mRNA - an ATGL inhibitor - in adipose tissue biopsies. In addition, pro-lipolytic ser563 HSL phosphorylations and protein kinase A (PKA) phosphorylation of PLIN1 (Perilipin-1) increased. The transcripts of ANGPTL4 (Angiopoietin-like 4) mRNA - a regulator of circulating triglycerides - were elevated by GC; as were CIDE (Cell-death Inducing DNA fragmentation factor-α-like Effector)-A and CIDE-C mRNA transcripts indicative of concurrent stimulation of lipolysis and lipogenesis. Finally GCs reduced insulin receptor phosphorylation, and Akt protein levels.CONCLUSIONS: High dose GC administration to humans leads to pro-lipolytic alterations of CGI-58, G0S2 and ANGPTL4 mRNA transcripts, increases PKA signaling to lipolysis and inhibits the insulin signal in adipose tissue. The increased CIDE-A and CIDE-C mRNA levels suggest concomitant stimulation of lipolysis and lipid storage.",

author = "Nilani Ramshanker and Niels Jessen and Voss, {Thomas Schmidt} and Pedersen, {Steen B{\o}nl{\o}kke} and J{\o}rgensen, {Jens Otto Lunde} and Nielsen, {Thomas Svava} and Jan Frystyk and Niels M{\o}ller",

note = "Copyright {\textcopyright} 2019. Published by Elsevier Inc.",

year = "2019",

month = oct,

doi = "10.1016/j.metabol.2019.06.013",

language = "English",

volume = "99",

pages = "1--10",

journal = "Metabolism: Clinical and Experimental",

issn = "0026-0495",

publisher = "Elsevier",

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TY - JOUR

T1 - Effects of short-term prednisolone treatment on indices of lipolysis and lipase signaling in abdominal adipose tissue in healthy humans

AU - Ramshanker, Nilani

AU - Jessen, Niels

AU - Voss, Thomas Schmidt

AU - Pedersen, Steen Bønløkke

AU - Jørgensen, Jens Otto Lunde

AU - Nielsen, Thomas Svava

AU - Frystyk, Jan

AU - Møller, Niels

PY - 2019/10

Y1 - 2019/10

N2 - BACKGROUND: Glucocorticoid (GC) excess increases lipolysis, circulating free fatty acid concentrations and lipid oxidation rates in humans. In vitro and animal studies have shown that GCs increase adipocyte ATGL and HSL mRNA contents and HSL phosphorylations, but the effects of GC on in vivo lipase signaling in humans are uncertain. Our study was designed to test how GC administration affects ATGL and HSL related signals in human adipose tissue.MATERIAL AND METHODS: Nine healthy young men underwent 5 days administration of 37.5 mg prednisolone/d in a randomized, double-blinded, placebo-controlled crossover design. At the end of each 5 d period the subjects were studied after an overnight fast for 6.5 h including a basal period and a 2½ h hyperinsulinemic euglycemic clamp. Adipose tissue biopsies were sampled from the abdominal subcutaneous adipose tissue at the end of the basal period and the clamp.RESULTS: GC treatment increased serum FFA concentrations and comparative gene identification-58 (CGI-58) mRNA - an ATGL activator - and decreased G0/G1 switch 2 gene (G0S2) mRNA - an ATGL inhibitor - in adipose tissue biopsies. In addition, pro-lipolytic ser563 HSL phosphorylations and protein kinase A (PKA) phosphorylation of PLIN1 (Perilipin-1) increased. The transcripts of ANGPTL4 (Angiopoietin-like 4) mRNA - a regulator of circulating triglycerides - were elevated by GC; as were CIDE (Cell-death Inducing DNA fragmentation factor-α-like Effector)-A and CIDE-C mRNA transcripts indicative of concurrent stimulation of lipolysis and lipogenesis. Finally GCs reduced insulin receptor phosphorylation, and Akt protein levels.CONCLUSIONS: High dose GC administration to humans leads to pro-lipolytic alterations of CGI-58, G0S2 and ANGPTL4 mRNA transcripts, increases PKA signaling to lipolysis and inhibits the insulin signal in adipose tissue. The increased CIDE-A and CIDE-C mRNA levels suggest concomitant stimulation of lipolysis and lipid storage.

AB - BACKGROUND: Glucocorticoid (GC) excess increases lipolysis, circulating free fatty acid concentrations and lipid oxidation rates in humans. In vitro and animal studies have shown that GCs increase adipocyte ATGL and HSL mRNA contents and HSL phosphorylations, but the effects of GC on in vivo lipase signaling in humans are uncertain. Our study was designed to test how GC administration affects ATGL and HSL related signals in human adipose tissue.MATERIAL AND METHODS: Nine healthy young men underwent 5 days administration of 37.5 mg prednisolone/d in a randomized, double-blinded, placebo-controlled crossover design. At the end of each 5 d period the subjects were studied after an overnight fast for 6.5 h including a basal period and a 2½ h hyperinsulinemic euglycemic clamp. Adipose tissue biopsies were sampled from the abdominal subcutaneous adipose tissue at the end of the basal period and the clamp.RESULTS: GC treatment increased serum FFA concentrations and comparative gene identification-58 (CGI-58) mRNA - an ATGL activator - and decreased G0/G1 switch 2 gene (G0S2) mRNA - an ATGL inhibitor - in adipose tissue biopsies. In addition, pro-lipolytic ser563 HSL phosphorylations and protein kinase A (PKA) phosphorylation of PLIN1 (Perilipin-1) increased. The transcripts of ANGPTL4 (Angiopoietin-like 4) mRNA - a regulator of circulating triglycerides - were elevated by GC; as were CIDE (Cell-death Inducing DNA fragmentation factor-α-like Effector)-A and CIDE-C mRNA transcripts indicative of concurrent stimulation of lipolysis and lipogenesis. Finally GCs reduced insulin receptor phosphorylation, and Akt protein levels.CONCLUSIONS: High dose GC administration to humans leads to pro-lipolytic alterations of CGI-58, G0S2 and ANGPTL4 mRNA transcripts, increases PKA signaling to lipolysis and inhibits the insulin signal in adipose tissue. The increased CIDE-A and CIDE-C mRNA levels suggest concomitant stimulation of lipolysis and lipid storage.

U2 - 10.1016/j.metabol.2019.06.013

DO - 10.1016/j.metabol.2019.06.013

M3 - Journal article

C2 - 31260678

SN - 0026-0495

VL - 99

SP - 1

EP - 10

JO - Metabolism: Clinical and Experimental

JF - Metabolism: Clinical and Experimental

ER -

Effects of short-term prednisolone treatment on indices of lipolysis and lipase signaling in abdominal adipose tissue in healthy humans

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