Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men

Abstract Insulin resistance is associated with high circulating level of complement factor C3. Animal studies suggest that improper complement activation mediates high-fat-diet-induced insulin resistance. Individuals born with low birth weight (LBW) are at increased risk of developing insulin resist...

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Autores principales:	Caroline Foghmar, Charlotte Brøns, Katrine Pilely, Allan Vaag, Peter Garred
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b67d2f118914fc7873438479e5435ae
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spelling	oai:doaj.org-article:8b67d2f118914fc7873438479e5435ae2021-12-02T12:30:35ZComplement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men10.1038/s41598-017-01382-32045-2322https://doaj.org/article/8b67d2f118914fc7873438479e5435ae2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01382-3https://doaj.org/toc/2045-2322Abstract Insulin resistance is associated with high circulating level of complement factor C3. Animal studies suggest that improper complement activation mediates high-fat-diet-induced insulin resistance. Individuals born with low birth weight (LBW) are at increased risk of developing insulin resistance. We hypothesized that high-fat overfeeding (HFO) increase circulating C3 and induce complement activation in a birth weight differential manner. Twenty LBW and 26 normal birth weight (NBW) young men were studied using a randomised crossover design. Insulin resistance was measured after a control-diet and after 5-days HFO by a hyperinsulinemic-euglycemic-clamp. Circulating C4, C3, ficolins, mannose-binding-lectin, complement activation products C3bc, terminal complement complex (TCC) and complement activation capacity were determined using turbidimetry and ELISA. HFO induced peripheral insulin resistance in LBW individuals only, while both groups had the same degree of hepatic insulin resistance after HFO. Viewing all individuals circulating levels of C4, C3, C3bc, TCC and complement activation capacity decreased paradoxically along the development of insulin resistance after HFO (P = 0.0015, P < 0.0001, P = 0.01, P < 0.0001, P = 0.0002, P < 0.0001, P = 0.0006). Birth weight did not influence these results. This might reflect a hitherto unrecognized down-regulatory mechanism of the complement system. More human studies are needed to understand the underlying physiology and the potential consequences of these findings.Caroline FoghmarCharlotte BrønsKatrine PilelyAllan VaagPeter GarredNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Caroline Foghmar Charlotte Brøns Katrine Pilely Allan Vaag Peter Garred Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men
description	Abstract Insulin resistance is associated with high circulating level of complement factor C3. Animal studies suggest that improper complement activation mediates high-fat-diet-induced insulin resistance. Individuals born with low birth weight (LBW) are at increased risk of developing insulin resistance. We hypothesized that high-fat overfeeding (HFO) increase circulating C3 and induce complement activation in a birth weight differential manner. Twenty LBW and 26 normal birth weight (NBW) young men were studied using a randomised crossover design. Insulin resistance was measured after a control-diet and after 5-days HFO by a hyperinsulinemic-euglycemic-clamp. Circulating C4, C3, ficolins, mannose-binding-lectin, complement activation products C3bc, terminal complement complex (TCC) and complement activation capacity were determined using turbidimetry and ELISA. HFO induced peripheral insulin resistance in LBW individuals only, while both groups had the same degree of hepatic insulin resistance after HFO. Viewing all individuals circulating levels of C4, C3, C3bc, TCC and complement activation capacity decreased paradoxically along the development of insulin resistance after HFO (P = 0.0015, P < 0.0001, P = 0.01, P < 0.0001, P = 0.0002, P < 0.0001, P = 0.0006). Birth weight did not influence these results. This might reflect a hitherto unrecognized down-regulatory mechanism of the complement system. More human studies are needed to understand the underlying physiology and the potential consequences of these findings.
format	article
author	Caroline Foghmar Charlotte Brøns Katrine Pilely Allan Vaag Peter Garred
author_facet	Caroline Foghmar Charlotte Brøns Katrine Pilely Allan Vaag Peter Garred
author_sort	Caroline Foghmar
title	Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men
title_short	Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men
title_full	Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men
title_fullStr	Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men
title_full_unstemmed	Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men
title_sort	complement factors c4 and c3 are down regulated in response to short term overfeeding in healthy young men
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8b67d2f118914fc7873438479e5435ae
work_keys_str_mv	AT carolinefoghmar complementfactorsc4andc3aredownregulatedinresponsetoshorttermoverfeedinginhealthyyoungmen AT charlottebrøns complementfactorsc4andc3aredownregulatedinresponsetoshorttermoverfeedinginhealthyyoungmen AT katrinepilely complementfactorsc4andc3aredownregulatedinresponsetoshorttermoverfeedinginhealthyyoungmen AT allanvaag complementfactorsc4andc3aredownregulatedinresponsetoshorttermoverfeedinginhealthyyoungmen AT petergarred complementfactorsc4andc3aredownregulatedinresponsetoshorttermoverfeedinginhealthyyoungmen
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Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young men

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