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Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle
AIMS/HYPOTHESIS: Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insu...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741704/ https://www.ncbi.nlm.nih.gov/pubmed/34704121 http://dx.doi.org/10.1007/s00125-021-05596-z |
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author | Sarabhai, Theresia Koliaki, Chrysi Mastrototaro, Lucia Kahl, Sabine Pesta, Dominik Apostolopoulou, Maria Wolkersdorfer, Martin Bönner, Anna C. Bobrov, Pavel Markgraf, Daniel F. Herder, Christian Roden, Michael |
author_facet | Sarabhai, Theresia Koliaki, Chrysi Mastrototaro, Lucia Kahl, Sabine Pesta, Dominik Apostolopoulou, Maria Wolkersdorfer, Martin Bönner, Anna C. Bobrov, Pavel Markgraf, Daniel F. Herder, Christian Roden, Michael |
author_sort | Sarabhai, Theresia |
collection | PubMed |
description | AIMS/HYPOTHESIS: Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling. METHODS: In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (R(d)) before and during hyperinsulinaemic–euglycaemic clamps with d-[6,6-(2)H(2)]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals. RESULTS: SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated R(d) (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine(1101)-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine(473)-phosphorylation of Akt more than SAF (p < 0.05). CONCLUSIONS/INTERPRETATION: Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling. TRIAL REGISTRATION: ClinicalTrials.gov.NCT01736202. FUNDING: German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05596-z. |
format | Online Article Text |
id | pubmed-8741704 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-87417042022-01-20 Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle Sarabhai, Theresia Koliaki, Chrysi Mastrototaro, Lucia Kahl, Sabine Pesta, Dominik Apostolopoulou, Maria Wolkersdorfer, Martin Bönner, Anna C. Bobrov, Pavel Markgraf, Daniel F. Herder, Christian Roden, Michael Diabetologia Article AIMS/HYPOTHESIS: Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling. METHODS: In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (R(d)) before and during hyperinsulinaemic–euglycaemic clamps with d-[6,6-(2)H(2)]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals. RESULTS: SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated R(d) (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine(1101)-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine(473)-phosphorylation of Akt more than SAF (p < 0.05). CONCLUSIONS/INTERPRETATION: Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling. TRIAL REGISTRATION: ClinicalTrials.gov.NCT01736202. FUNDING: German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05596-z. Springer Berlin Heidelberg 2021-10-26 2022 /pmc/articles/PMC8741704/ /pubmed/34704121 http://dx.doi.org/10.1007/s00125-021-05596-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sarabhai, Theresia Koliaki, Chrysi Mastrototaro, Lucia Kahl, Sabine Pesta, Dominik Apostolopoulou, Maria Wolkersdorfer, Martin Bönner, Anna C. Bobrov, Pavel Markgraf, Daniel F. Herder, Christian Roden, Michael Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle |
title | Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle |
title_full | Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle |
title_fullStr | Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle |
title_full_unstemmed | Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle |
title_short | Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle |
title_sort | dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741704/ https://www.ncbi.nlm.nih.gov/pubmed/34704121 http://dx.doi.org/10.1007/s00125-021-05596-z |
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