Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism
Objective: Human energy metabolism is under the regulation of the molecular circadian clock; we recently reported that mitochondrial respiration displays a day-night rhythm under study conditions that are similar to real life. Mitochondria are interconnected with lipid droplets, which are of importa...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877820300636 |
| _version_ | 1830513335998611456 |
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| author | Ntsiki M. Held Jakob Wefers Michel van Weeghel Sabine Daemen Jan Hansen Frédéric M. Vaz Dirk van Moorsel Matthijs K.C. Hesselink Riekelt H. Houtkooper Patrick Schrauwen |
| author_facet | Ntsiki M. Held Jakob Wefers Michel van Weeghel Sabine Daemen Jan Hansen Frédéric M. Vaz Dirk van Moorsel Matthijs K.C. Hesselink Riekelt H. Houtkooper Patrick Schrauwen |
| author_sort | Ntsiki M. Held |
| collection | DOAJ |
| description | Objective: Human energy metabolism is under the regulation of the molecular circadian clock; we recently reported that mitochondrial respiration displays a day-night rhythm under study conditions that are similar to real life. Mitochondria are interconnected with lipid droplets, which are of importance in fuel utilization and play a role in muscle insulin sensitivity. Here, we investigated if skeletal muscle lipid content and composition also display day-night rhythmicity in healthy, lean volunteers. Methods: Skeletal muscle biopsies were obtained from 12 healthy lean male volunteers every 5 h over a 24 h period. Volunteers were provided with standardized meals, and biopsies were taken 4.5 h after each last meal. Lipid droplet size and number were investigated by confocal microscopy. Additionally, the muscle lipidome was assessed using UPLC/HRMS-based semi-targeted lipidomics. Results: Confocal microscopy revealed diurnal differences in intramyocellular lipid content (P < 0.05) and lipid droplet size in oxidative type 1 muscle fibers (P < 0.01). Lipidomics analysis revealed that 13% of all detected lipids displayed significant day-night rhythmicity. The most rhythmic lipid species were glycerophospholipids and diacylglycerols (DAG), with the latter being the largest fraction (>50% of all rhythmic species). DAG levels showed a day-night pattern with a trough at 1 PM and a peak at 4 AM. Conclusions: Using two distinct methods, our findings show that myocellular lipid content and whole muscle lipid composition vary across the day-night cycle under normal living conditions. In particular, day-night rhythmicity was present in over half of the DAG lipid species. Future studies are needed to investigate whether rhythmicity in DAG is functionally related to insulin sensitivity and how this might be altered in prediabetes. |
| first_indexed | 2024-12-22T02:42:34Z |
| format | Article |
| id | doaj.art-8c9fb2bf7c134bef93031cd3d8361096 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-22T02:42:34Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-8c9fb2bf7c134bef93031cd3d83610962022-12-21T18:41:36ZengElsevierMolecular Metabolism2212-87782020-07-0137100989Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolismNtsiki M. Held0Jakob Wefers1Michel van Weeghel2Sabine Daemen3Jan Hansen4Frédéric M. Vaz5Dirk van Moorsel6Matthijs K.C. Hesselink7Riekelt H. Houtkooper8Patrick Schrauwen9Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, the NetherlandsLaboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsDiabetes Research Center, Washington University, St. Louis, MO 63110, USADepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, the NetherlandsLaboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, the NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, the NetherlandsLaboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Corresponding author. Laboratory Genetic Metabolic Diseases, Amsterdam UMC, location AMC Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, the Netherlands; Corresponding author. Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, P.O. Box 616, 6200 MD Maastricht, the Netherlands.Objective: Human energy metabolism is under the regulation of the molecular circadian clock; we recently reported that mitochondrial respiration displays a day-night rhythm under study conditions that are similar to real life. Mitochondria are interconnected with lipid droplets, which are of importance in fuel utilization and play a role in muscle insulin sensitivity. Here, we investigated if skeletal muscle lipid content and composition also display day-night rhythmicity in healthy, lean volunteers. Methods: Skeletal muscle biopsies were obtained from 12 healthy lean male volunteers every 5 h over a 24 h period. Volunteers were provided with standardized meals, and biopsies were taken 4.5 h after each last meal. Lipid droplet size and number were investigated by confocal microscopy. Additionally, the muscle lipidome was assessed using UPLC/HRMS-based semi-targeted lipidomics. Results: Confocal microscopy revealed diurnal differences in intramyocellular lipid content (P < 0.05) and lipid droplet size in oxidative type 1 muscle fibers (P < 0.01). Lipidomics analysis revealed that 13% of all detected lipids displayed significant day-night rhythmicity. The most rhythmic lipid species were glycerophospholipids and diacylglycerols (DAG), with the latter being the largest fraction (>50% of all rhythmic species). DAG levels showed a day-night pattern with a trough at 1 PM and a peak at 4 AM. Conclusions: Using two distinct methods, our findings show that myocellular lipid content and whole muscle lipid composition vary across the day-night cycle under normal living conditions. In particular, day-night rhythmicity was present in over half of the DAG lipid species. Future studies are needed to investigate whether rhythmicity in DAG is functionally related to insulin sensitivity and how this might be altered in prediabetes.http://www.sciencedirect.com/science/article/pii/S2212877820300636Circadian clockLipidomicsLipid metabolismHuman skeletal muscle |
| spellingShingle | Ntsiki M. Held Jakob Wefers Michel van Weeghel Sabine Daemen Jan Hansen Frédéric M. Vaz Dirk van Moorsel Matthijs K.C. Hesselink Riekelt H. Houtkooper Patrick Schrauwen Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism Molecular Metabolism Circadian clock Lipidomics Lipid metabolism Human skeletal muscle |
| title | Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism |
| title_full | Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism |
| title_fullStr | Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism |
| title_full_unstemmed | Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism |
| title_short | Skeletal muscle in healthy humans exhibits a day-night rhythm in lipid metabolism |
| title_sort | skeletal muscle in healthy humans exhibits a day night rhythm in lipid metabolism |
| topic | Circadian clock Lipidomics Lipid metabolism Human skeletal muscle |
| url | http://www.sciencedirect.com/science/article/pii/S2212877820300636 |
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