Increased lipolysis after infusion of acylated ghrelin: a randomized, double-blinded placebo-controlled trial in hypopituitary patients

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Increased lipolysis after infusion of acylated ghrelin : a randomized, double-blinded placebo-controlled trial in hypopituitary patients. / Lauritzen, Esben Stistrup; Jorgensen, Jens Otto Lunde; Møller, Niels; Nielsen, Soren; Vestergaard, Esben Thyssen.

I: Clinical Endocrinology, Bind 93, Nr. 6, 12.2020, s. 672-677.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{c623a042b25743c89cf3dae8c72d3c90,
title = "Increased lipolysis after infusion of acylated ghrelin: a randomized, double-blinded placebo-controlled trial in hypopituitary patients",
abstract = "Context Acylated ghrelin increases growth hormone (GH) and adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary gland. Additionally, it increases free fatty acid levels independently of GH and ACTH, but the impact of ghrelin on fatty acid turnover has not been determined. This study was designed to test whether acylated ghrelin directly increases the turnover rate of fatty acids. Design Eight hypopituitary patients on stable replacement with GH and hydrocortisone were included in a randomized, double-blinded, placebo-controlled crossover study including two study days: (a) infusion of acylated ghrelin and (b) infusion of saline. The study day comprised a basal period (t = 0-120 minutes) and a hyperinsulinaemic-euglycemic clamp period (t = 120-300 minutes). Whole-body lipolysis was estimated att = 90-120 andt = 270-300 minutes with a palmitate isotope dilution technique. Results Infusion of acylated ghrelin resulted in 10 times increased total ghrelin area under the curve (AUC) levels in the basal period and 15 times increased AUC levels in the clamp period compared with saline infusion (P <.001). GH(AUC)levels were largely unaffected by ghrelin compared to saline infusion during both the basal and clamp period, but cortisol(AUC)levels increased by 15% after ghrelin compared to saline infusion in the basal period (P = .03). Palmitate turnover was increased by 43% in the basal period (difference: 77 (20) mu mol/min,P = .01) and unchanged in the clamp period (difference 0.9 (17) mu mol/min,P = 1.0) after ghrelin compared to saline infusion. Conclusions Our results support the hypothesis that pharmacological levels of acylated ghrelin directly activate lipolysis at the whole-body level.",
keywords = "acyl ghrelin, acylated ghrelin, ghrelin, lipolysis, palmitate turnover, GROWTH-HORMONE, SECRETION, INSULIN, CORTISOL, GLYCEROL, PEPTIDE, GLUCOSE",
author = "Lauritzen, {Esben Stistrup} and Jorgensen, {Jens Otto Lunde} and Niels M{\o}ller and Soren Nielsen and Vestergaard, {Esben Thyssen}",
year = "2020",
month = dec,
doi = "10.1111/cen.14290",
language = "English",
volume = "93",
pages = "672--677",
journal = "Clinical Endocrinology",
issn = "0300-0664",
publisher = "Wiley-Blackwell Publishing Ltd.",
number = "6",

}

RIS

TY - JOUR

T1 - Increased lipolysis after infusion of acylated ghrelin

T2 - a randomized, double-blinded placebo-controlled trial in hypopituitary patients

AU - Lauritzen, Esben Stistrup

AU - Jorgensen, Jens Otto Lunde

AU - Møller, Niels

AU - Nielsen, Soren

AU - Vestergaard, Esben Thyssen

PY - 2020/12

Y1 - 2020/12

N2 - Context Acylated ghrelin increases growth hormone (GH) and adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary gland. Additionally, it increases free fatty acid levels independently of GH and ACTH, but the impact of ghrelin on fatty acid turnover has not been determined. This study was designed to test whether acylated ghrelin directly increases the turnover rate of fatty acids. Design Eight hypopituitary patients on stable replacement with GH and hydrocortisone were included in a randomized, double-blinded, placebo-controlled crossover study including two study days: (a) infusion of acylated ghrelin and (b) infusion of saline. The study day comprised a basal period (t = 0-120 minutes) and a hyperinsulinaemic-euglycemic clamp period (t = 120-300 minutes). Whole-body lipolysis was estimated att = 90-120 andt = 270-300 minutes with a palmitate isotope dilution technique. Results Infusion of acylated ghrelin resulted in 10 times increased total ghrelin area under the curve (AUC) levels in the basal period and 15 times increased AUC levels in the clamp period compared with saline infusion (P <.001). GH(AUC)levels were largely unaffected by ghrelin compared to saline infusion during both the basal and clamp period, but cortisol(AUC)levels increased by 15% after ghrelin compared to saline infusion in the basal period (P = .03). Palmitate turnover was increased by 43% in the basal period (difference: 77 (20) mu mol/min,P = .01) and unchanged in the clamp period (difference 0.9 (17) mu mol/min,P = 1.0) after ghrelin compared to saline infusion. Conclusions Our results support the hypothesis that pharmacological levels of acylated ghrelin directly activate lipolysis at the whole-body level.

AB - Context Acylated ghrelin increases growth hormone (GH) and adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary gland. Additionally, it increases free fatty acid levels independently of GH and ACTH, but the impact of ghrelin on fatty acid turnover has not been determined. This study was designed to test whether acylated ghrelin directly increases the turnover rate of fatty acids. Design Eight hypopituitary patients on stable replacement with GH and hydrocortisone were included in a randomized, double-blinded, placebo-controlled crossover study including two study days: (a) infusion of acylated ghrelin and (b) infusion of saline. The study day comprised a basal period (t = 0-120 minutes) and a hyperinsulinaemic-euglycemic clamp period (t = 120-300 minutes). Whole-body lipolysis was estimated att = 90-120 andt = 270-300 minutes with a palmitate isotope dilution technique. Results Infusion of acylated ghrelin resulted in 10 times increased total ghrelin area under the curve (AUC) levels in the basal period and 15 times increased AUC levels in the clamp period compared with saline infusion (P <.001). GH(AUC)levels were largely unaffected by ghrelin compared to saline infusion during both the basal and clamp period, but cortisol(AUC)levels increased by 15% after ghrelin compared to saline infusion in the basal period (P = .03). Palmitate turnover was increased by 43% in the basal period (difference: 77 (20) mu mol/min,P = .01) and unchanged in the clamp period (difference 0.9 (17) mu mol/min,P = 1.0) after ghrelin compared to saline infusion. Conclusions Our results support the hypothesis that pharmacological levels of acylated ghrelin directly activate lipolysis at the whole-body level.

KW - acyl ghrelin

KW - acylated ghrelin

KW - ghrelin

KW - lipolysis

KW - palmitate turnover

KW - GROWTH-HORMONE

KW - SECRETION

KW - INSULIN

KW - CORTISOL

KW - GLYCEROL

KW - PEPTIDE

KW - GLUCOSE

UR - http://www.scopus.com/inward/record.url?scp=85088877446&partnerID=8YFLogxK

U2 - 10.1111/cen.14290

DO - 10.1111/cen.14290

M3 - Journal article

C2 - 32975853

VL - 93

SP - 672

EP - 677

JO - Clinical Endocrinology

JF - Clinical Endocrinology

SN - 0300-0664

IS - 6

ER -