Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.

<h4>Background</h4>Fibroblast growth factor (FGF)-21 is a novel regulator of glucose and lipid metabolism. Recently, increased FGF-21 mRNA expression in muscle was found in patients with type 2 diabetes, but the role for FGF-21 in muscle is not well understood. Patients with HIV-infectio...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Birgitte Lindegaard, Thine Hvid, Thomas Grøndahl, Christian Frosig, Jan Gerstoft, Pernille Hojman, Bente Klarlund Pedersen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/02dde318e27043358bcd651a53000ef9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:02dde318e27043358bcd651a53000ef9
record_format	dspace
spelling	oai:doaj.org-article:02dde318e27043358bcd651a53000ef92021-11-18T07:52:23ZExpression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.1932-620310.1371/journal.pone.0055632https://doaj.org/article/02dde318e27043358bcd651a53000ef92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23533568/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Fibroblast growth factor (FGF)-21 is a novel regulator of glucose and lipid metabolism. Recently, increased FGF-21 mRNA expression in muscle was found in patients with type 2 diabetes, but the role for FGF-21 in muscle is not well understood. Patients with HIV-infection and lipodystrophy are characterised by various degree of lipid-driven insulin resistance. We hypothesized that muscle FGF-21 mRNA would be altered in HIV patients with lipodystrophy.<h4>Design</h4>Twenty-five HIV-infected men with lipodystrophy (LD) and 15 age-matched healthy controls, received an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp (50 mU/m2/min) combined with 6,6-H2 glucose infusion. Muscle biopsies were obtained and FGF-21 mRNA and glycogen synthase (GS) activity were measured.<h4>Results</h4>Subjects with HIV were insulin resistant compared with non-HIV subjects. Compared to controls, HIV subjects demonstrated a twofold increase of plasma FGF-21 from 70.4±56.8 pg/ml vs 109.1±71.8 pg/ml, respectively (p = 0.04) and an eight-fold increase in muscular FGF-21 mRNA expression (p = 0.001). Muscle FGF-21 mRNA correlated inversely with the rate of disappearance of glucose during insulin clamp (r = -0.54, p = 0.0009), and the GS fractional velocity in muscle (r = -0.39, p = 0.03), and directly with fasting insulin (r = 0.50, p = 0.0022), HOMA-IR (r = 0.47, p = 0.004), triglycerides (r = 0.60. P = 0.0001), waist-to-hip ratio (r = 0.51, p = 0.0001) and limb fat mass (-0.46, p = 0.004), but not to plasma FGF-21.<h4>Conclusion</h4>FGF-21 mRNA is increased in skeletal muscle in HIV patients and correlates to whole-body (primarily reflecting muscle) insulin resistance, but not to plasma FGF-21. Those findings add to the evidence that FGF-21 is a myokine and may suggest that muscle FGF-21 is working in a local manner.Birgitte LindegaardThine HvidThomas GrøndahlChristian FrosigJan GerstoftPernille HojmanBente Klarlund PedersenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e55632 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Birgitte Lindegaard Thine Hvid Thomas Grøndahl Christian Frosig Jan Gerstoft Pernille Hojman Bente Klarlund Pedersen Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.
description	<h4>Background</h4>Fibroblast growth factor (FGF)-21 is a novel regulator of glucose and lipid metabolism. Recently, increased FGF-21 mRNA expression in muscle was found in patients with type 2 diabetes, but the role for FGF-21 in muscle is not well understood. Patients with HIV-infection and lipodystrophy are characterised by various degree of lipid-driven insulin resistance. We hypothesized that muscle FGF-21 mRNA would be altered in HIV patients with lipodystrophy.<h4>Design</h4>Twenty-five HIV-infected men with lipodystrophy (LD) and 15 age-matched healthy controls, received an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp (50 mU/m2/min) combined with 6,6-H2 glucose infusion. Muscle biopsies were obtained and FGF-21 mRNA and glycogen synthase (GS) activity were measured.<h4>Results</h4>Subjects with HIV were insulin resistant compared with non-HIV subjects. Compared to controls, HIV subjects demonstrated a twofold increase of plasma FGF-21 from 70.4±56.8 pg/ml vs 109.1±71.8 pg/ml, respectively (p = 0.04) and an eight-fold increase in muscular FGF-21 mRNA expression (p = 0.001). Muscle FGF-21 mRNA correlated inversely with the rate of disappearance of glucose during insulin clamp (r = -0.54, p = 0.0009), and the GS fractional velocity in muscle (r = -0.39, p = 0.03), and directly with fasting insulin (r = 0.50, p = 0.0022), HOMA-IR (r = 0.47, p = 0.004), triglycerides (r = 0.60. P = 0.0001), waist-to-hip ratio (r = 0.51, p = 0.0001) and limb fat mass (-0.46, p = 0.004), but not to plasma FGF-21.<h4>Conclusion</h4>FGF-21 mRNA is increased in skeletal muscle in HIV patients and correlates to whole-body (primarily reflecting muscle) insulin resistance, but not to plasma FGF-21. Those findings add to the evidence that FGF-21 is a myokine and may suggest that muscle FGF-21 is working in a local manner.
format	article
author	Birgitte Lindegaard Thine Hvid Thomas Grøndahl Christian Frosig Jan Gerstoft Pernille Hojman Bente Klarlund Pedersen
author_facet	Birgitte Lindegaard Thine Hvid Thomas Grøndahl Christian Frosig Jan Gerstoft Pernille Hojman Bente Klarlund Pedersen
author_sort	Birgitte Lindegaard
title	Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.
title_short	Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.
title_full	Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.
title_fullStr	Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.
title_full_unstemmed	Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.
title_sort	expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with hiv.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/02dde318e27043358bcd651a53000ef9
work_keys_str_mv	AT birgittelindegaard expressionoffibroblastgrowthfactor21inmuscleisassociatedwithlipodystrophyinsulinresistanceandlipiddisturbancesinpatientswithhiv AT thinehvid expressionoffibroblastgrowthfactor21inmuscleisassociatedwithlipodystrophyinsulinresistanceandlipiddisturbancesinpatientswithhiv AT thomasgrøndahl expressionoffibroblastgrowthfactor21inmuscleisassociatedwithlipodystrophyinsulinresistanceandlipiddisturbancesinpatientswithhiv AT christianfrosig expressionoffibroblastgrowthfactor21inmuscleisassociatedwithlipodystrophyinsulinresistanceandlipiddisturbancesinpatientswithhiv AT jangerstoft expressionoffibroblastgrowthfactor21inmuscleisassociatedwithlipodystrophyinsulinresistanceandlipiddisturbancesinpatientswithhiv AT pernillehojman expressionoffibroblastgrowthfactor21inmuscleisassociatedwithlipodystrophyinsulinresistanceandlipiddisturbancesinpatientswithhiv AT benteklarlundpedersen expressionoffibroblastgrowthfactor21inmuscleisassociatedwithlipodystrophyinsulinresistanceandlipiddisturbancesinpatientswithhiv
_version_	1718422829698908160

Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.

Ejemplares similares