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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-01382-3 |
| _version_ | 1818752494557200384 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T04:52:21Z |
| format | Article |
| id | doaj.art-8b67d2f118914fc7873438479e5435ae |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:52:21Z |
| publishDate | 2017-04-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-8b67d2f118914fc7873438479e5435ae2022-12-21T21:20:22ZengNature PortfolioScientific Reports2045-23222017-04-017111110.1038/s41598-017-01382-3Complement factors C4 and C3 are down regulated in response to short term overfeeding in healthy young menCaroline Foghmar0Charlotte Brøns1Katrine Pilely2Allan Vaag3Peter Garred4Rigshospitalet, Faculty of Health and Medical Sciences University of Copenhagen, Laboratory of Molecular Medicine, Department of Clinical ImmunologyRigshospitalet, Faculty of Health and Medical Sciences University of Copenhagen, Department of Endocrinology (Diabetes and metabolism)Rigshospitalet, Faculty of Health and Medical Sciences University of Copenhagen, Laboratory of Molecular Medicine, Department of Clinical ImmunologyRigshospitalet, Faculty of Health and Medical Sciences University of Copenhagen, Department of Endocrinology (Diabetes and metabolism)Rigshospitalet, Faculty of Health and Medical Sciences University of Copenhagen, Laboratory of Molecular Medicine, Department of Clinical ImmunologyAbstract 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.https://doi.org/10.1038/s41598-017-01382-3 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-01382-3 |
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