Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle.
| Title: | Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle. |
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| Authors: | Wefers J; Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; van Moorsel D; Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; Division of Endocrinology, Department of Internal Medicine, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; Hansen J; Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; Connell NJ; Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; Havekes B; Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; Division of Endocrinology, Department of Internal Medicine, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; Hoeks J; Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; van Marken Lichtenbelt WD; Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; Duez H; Université de Lille-European Genomic Institute for Diabetes, Centre Hospitalier Universitaire Lille, Institut Pasteur de Lille, Inserm UMR 1011, 59019 Lille, France.; Phielix E; Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; Kalsbeek A; Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, 1105 BA Amsterdam, The Netherlands.; Boekschoten MV; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, The Netherlands.; Hooiveld GJ; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, The Netherlands.; Hesselink MKC; Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.; Kersten S; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, The Netherlands.; Staels B; Université de Lille-European Genomic Institute for Diabetes, Centre Hospitalier Universitaire Lille, Institut Pasteur de Lille, Inserm UMR 1011, 59019 Lille, France.; Scheer FAJL; Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115.; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115.; Schrauwen P; Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands; p.schrauwen@maastrichtuniversity.nl. |
| Source: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Jul 24; Vol. 115 (30), pp. 7789-7794. Date of Electronic Publication: 2018 Jul 09. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : National Academy of Sciences |
| MeSH Terms: | Gene Expression Profiling* ; Heart* ; Insulin Resistance*; Diabetes Mellitus, Type 2/*blood ; Fatty Acids/*blood ; Muscle, Skeletal/*metabolism ; Obesity/*blood; Diabetes Mellitus, Type 2/pathology ; Muscle, Skeletal/pathology ; Obesity/pathology ; Adult ; Humans ; Male |
| Abstract: | Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes. However, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and the muscle molecular circadian clock have never been studied in humans. Here, we investigated insulin sensitivity and muscle metabolism in 14 healthy young lean men [age 22.4 ± 2.8 years; body mass index (BMI) 22.3 ± 2.1 kg/m2 (mean ± SD)] after a 3-d control protocol and a 3.5-d misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that short-term circadian misalignment results in a significant decrease in muscle insulin sensitivity due to a reduced skeletal muscle nonoxidative glucose disposal (rate of disappearance: 23.7 ± 2.4 vs. 18.4 ± 1.4 mg/kg per minute; control vs. misalignment; P = 0.024). Fasting glucose and free fatty acid levels as well as sleeping metabolic rate were higher during circadian misalignment. Molecular analysis of skeletal muscle biopsies revealed that the molecular circadian clock was not aligned to the inverted behavioral cycle, and transcriptome analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misalignment. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.; (Copyright © 2018 the Author(s). Published by PNAS.) |
| Competing Interests: | Conflict of interest statement: F.A.J.L.S. has received speaker fees from Bayer Healthcare, Sentara Healthcare, Kellogg, Philips, and Vanda Pharmaceuticals. |
| Comments: | Comment in: Nat Rev Endocrinol. 2018 Sep;14(9):503. doi: 10.1038/s41574-018-0074-5.. (PMID: 30042395); Comment in: Nat Rev Endocrinol. 2023 Sep;19(9):502. doi: 10.1038/s41574-023-00875-8.. (PMID: 37474747) |
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| Grant Information: | R01 DK099512 United States DK NIDDK NIH HHS; R01 HL118601 United States HL NHLBI NIH HHS; R01 DK102696 United States DK NIDDK NIH HHS; R01 HL140574 United States HL NHLBI NIH HHS; R01 DK105072 United States DK NIDDK NIH HHS |
| Contributed Indexing: | Keywords: circadian misalignment; diabetes; insulin sensitivity; shift work; skeletal muscle |
| Substance Nomenclature: | 0 (Fatty Acids) |
| Entry Date(s): | Date Created: 20180711 Date Completed: 20180917 Latest Revision: 20230926 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC6065021 |
| DOI: | 10.1073/pnas.1722295115 |
| PMID: | 29987027 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't