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Shuhui Ma Laboratory of Anatomy of Domestic Animals, College of Animal Medicine, China Agricultural University, Haidian, Beijing, China

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Zixu Wang Laboratory of Anatomy of Domestic Animals, College of Animal Medicine, China Agricultural University, Haidian, Beijing, China

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Jing Cao Laboratory of Anatomy of Domestic Animals, College of Animal Medicine, China Agricultural University, Haidian, Beijing, China

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Yulan Dong Laboratory of Anatomy of Domestic Animals, College of Animal Medicine, China Agricultural University, Haidian, Beijing, China

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Yaoxing Chen Laboratory of Anatomy of Domestic Animals, College of Animal Medicine, China Agricultural University, Haidian, Beijing, China

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the biological clock oscillators, the pineal gland secretes melatonin into the blood with high level during the subjective night and low level during the subjective day ( 2 ) and is a typical model system for the study of circadian rhythm. Melatonin

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Mohammed S Albreiki Department of Biochemistry and Physiology, Centre for Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK

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Benita Middleton Department of Biochemistry and Physiology, Centre for Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK

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Shelagh M Hampton Department of Biochemistry and Physiology, Centre for Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK

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). Melatonin is considered the classical phase marker for assessing the timing of the mammalian biological clock. The SCN drives the daily rhythms in hormone concentrations such as insulin, glucagon, corticosterone ( 4 , 5 , 6 ) and enzymes involved in lipid

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Junhui Zhang J Zhang, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

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Hongyan Zhang H Zhang, Department of Histology and Embryology, Anhui Medical University, Hefei, China

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Bao Guo B Guo, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

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Jun Yang J Yang, Anhui Medical University, Hefei, China

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Renxiang Yu R Yu, Anhui Medical University, Hefei, China

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Wenxiu Chen W Chen, Department of Histology and Embryology, Anhui Medical University, Hefei, China

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Muxin Zhai M Zhai, Anhui Medical University, Hefei, China

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Cao Yuhan C Yuhan, Anhui Medical University, Hefei, China

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Yajing Liu Y Liu, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, China

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Qiang Hong Q Hong, Department of Histology and Embryology, Anhui Medical University, Hefei, 230032, China

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Fenfen Xie F Xie, Department of Histology and Embryology, Anhui Medical University, Hefei, 230032, China

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The elevated level of hepatic oxidative stress (OS) in polycystic ovary syndrome (PCOS) is one of the important causes of liver abnormalities. Therefore, decreasing the level of hepatic OS in PCOS is beneficial to reduce the risk of PCOS-related liver diseases. Melatonin (MT), recognized as a potent antioxidant. Nevertheless, the efficacy of MT in alleviating hepatic OS associated with PCOS is yet to be established, and the precise mechanisms through which MT exerts its antioxidant effects remain to be fully elucidated. The aim of this study was to explore the potential mechanism by which MT reduces hepatic OS in PCOS. First, we detected elevated OS levels in the PCOS samples. Subsequently, with MT pretreatment, we discovered that MT could significantly diminish the levels of OS, liver triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST),while concurrently ameliorating mitochondrial structural damage in PCOS liver. Furthermore, we identified elevated autophagy levels in the liver of PCOS rats and an inhibition of the Keap1-Nrf2 pathway. Through MT pretreatment, the expression of LC3 was significantly decreased, while the Keap1-Nrf2 pathway was activated. Our study showed that MT could affect the Nrf2 pathway dependent on the P62/LC3 autophagy pathway, thereby attenuating hepatic OS in PCOS. These findings offer novel insights and research avenues for the study of PCOS-related liver diseases.

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Henryk F Urbanski Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, USA
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA
Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, Oregon, USA

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Kevin Mueller Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA

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Cynthia L Bethea Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, USA
Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, USA
Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon, USA

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Like women, old female rhesus macaques undergo menopause and show many of the same age-associated changes, including perturbed activity/rest cycles and altered circulating levels of many hormones. Previous studies showed that administration of an estrogen agonist increased activity in female monkeys, that hormone therapy (HT) increased activity in postmenopausal women and that obesity decreased activity in women. The present study sought to determine if postmenopausal activity and circulating hormone levels also respond to HT when monkeys are fed a high-fat, high-sugar Western style diet (WSD). Old female rhesus macaques were ovo-hysterectomized (OvH) to induce surgical menopause and fed a WSD for 2 years. Half of the animals received estradiol-17β (E), beginning immediately after OvH, while the other half received placebo. Animals in both groups showed an increase in body weight and a decrease in overall activity levels. These changes were associated with a rise in both daytime and nocturnal serum leptin concentrations, but there was no change in serum concentrations of either cortisol or dehydroepiandrosterone sulfate (DHEAS). These data suggest that 2 years of HT has little or no effect on locomotor activity or circadian hormone patterns in menopausal macaques fed an obesogenic diet.

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Cheryl M Isherwood Section of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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M Denise Robertson Section of Metabolic Medicine, Food and Macronutrients, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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Debra J Skene Section of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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Jonathan D Johnston Section of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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significant difference in plasma leptin or clock gene expression in adipose tissue from the upper gluteal region ( 26 , 27 ). There were, however, significant differences in rhythms of plasma melatonin and metabolite concentration between the groups ( 27

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Josef Köhrle Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institut für Experimentelle Endokrinologie, Berlin, Germany

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Martina Rauner Department of Medicine III, Universitätsklinikum Dresden, Technische Universität Dresden, Dresden, Germany
Center for Healthy Aging, Universitätsklinikum Dresden, Technische Universität Dresden, Dresden, Germany

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Susan A Lanham-New Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK

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receptor in retinal ganglion cells instructs the circadian clock of the suprachiasmatic nucleus and suppresses epiphysial melatonin production, as well as melanophore activation in the skin. This special series on 100 Years of Vitamin D, published in

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Shanlee M Davis Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Rhianna Urban Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

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Angelo D’Alessandro Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Julie A Reisz Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Christine L Chan Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Megan Kelsey Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Susan Howell Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Nicole Tartaglia Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Philip Zeitler Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Peter Baker II Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

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only are suggested to be biomarkers of disrupted mitochondrial metabolism but also may contribute to the progression of insulin resistance. A few studies have investigated specific metabolites in KS, such as steroids, melatonin, and markers of bone

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Julie Smith Department of Clinical Biochemistry (KB3014), Department of Technology, Department of Clinical Biochemistry, Department of Biomedical Sciences, Department of Clinical Medicine, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark

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Jan Fahrenkrug Department of Clinical Biochemistry (KB3014), Department of Technology, Department of Clinical Biochemistry, Department of Biomedical Sciences, Department of Clinical Medicine, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark

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Henrik L Jørgensen Department of Clinical Biochemistry (KB3014), Department of Technology, Department of Clinical Biochemistry, Department of Biomedical Sciences, Department of Clinical Medicine, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark

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Christina Christoffersen Department of Clinical Biochemistry (KB3014), Department of Technology, Department of Clinical Biochemistry, Department of Biomedical Sciences, Department of Clinical Medicine, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark
Department of Clinical Biochemistry (KB3014), Department of Technology, Department of Clinical Biochemistry, Department of Biomedical Sciences, Department of Clinical Medicine, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark

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Jens P Goetze Department of Clinical Biochemistry (KB3014), Department of Technology, Department of Clinical Biochemistry, Department of Biomedical Sciences, Department of Clinical Medicine, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark
Department of Clinical Biochemistry (KB3014), Department of Technology, Department of Clinical Biochemistry, Department of Biomedical Sciences, Department of Clinical Medicine, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark

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D Folkard S Hampton S Deacon S English J Ribeiro D Taylor K . Effects of the endogenous clock and sleep time on melatonin, insulin, glucose and lipid metabolism . Journal of Endocrinology 1998

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Brendan J Nolan Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia

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Aviva S Frydman Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia

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Shalem Y Leemaqz College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia

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Meg Carroll Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia

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Mathis Grossmann Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia

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Jeffrey D Zajac Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia

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Ada S Cheung Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine (Austin Health), University of Melbourne, Heidelberg, Victoria, Australia

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’Hermite-Balériaux M Kerkhofs M Copinschi G . Progesterone prevents sleep disturbances and modulates GH, TSH, and melatonin secretion in postmenopausal women . Journal of Clinical Endocrinology and Metabolism 2011 96 E614 – E623 . ( https://doi.org/10.1210/jc

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Robert Maidstone Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

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Martin K Rutter Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
Diabetes, Endocrinology and Metabolism Centre, Manchester University NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, UK

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Thomas Marjot Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
Oxford Liver Unit, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, UK

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David W Ray Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
NIHR Oxford Health Biomedical Research Centre, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK

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Matthew Baxter Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
NIHR Oxford Health Biomedical Research Centre, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK

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correlate with dim-light melatonin onset and sleep timing ( 10 , 11 , 12 ). Statistical analysis Multivariate logistic regression models compared adjusted odds ratios and corresponding 95% asymptotic confidence intervals for NAFLD outcomes in

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