Adiponectin regulates the circadian rhythm of glucose and lipid metabolism

Journal of Endocrinology, Год журнала: 2022, Номер 254(2), С. 121 - 133

Опубликована: Июнь 6, 2022

Adiponectin is a cytokine secreted from adipocytes and regulates metabolism. Although serum adiponectin levels show diurnal variations, it not clear if the effects of are time-dependent. Therefore, this study conducted locomotor activity analyses various metabolic studies using knockout (APN (-/-)) APN (+/+) mice to understand whether circadian rhythm glucose lipid We observed that gene deficiency does affect rhythmicity core clock genes expression in several peripheral tissues. In contrast, alters rhythms liver results loss time dependency very-low-density lipoprotein-triglyceride secretion liver. addition, whole-body tolerance (-/-) was normal at CT10 but reduced CT22, compared mice. The decreased CT22 associated with insulin hyposecretion vivo. gluconeogenesis higher than throughout day. These indicate part metabolism

Язык: Английский

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Rewiring of liver diurnal transcriptome rhythms by triiodothyronine (T3) supplementation

eLife, Год журнала: 2022, Номер 11

Опубликована: Июль 27, 2022

Diurnal (i.e., 24 hr) physiological rhythms depend on transcriptional programs controlled by a set of circadian clock genes/proteins. Systemic factors like humoral and neuronal signals, oscillations in body temperature, food intake align with external time. Thyroid hormones (THs) are major regulators target processes such as energy metabolism, but little is known about how fluctuations TH levels affect the coordination tissue physiology. In this study, high triiodothyronine (T 3 ) state was induced mice supplementing T drinking water, which affected oxygen consumption time-of-day-dependent manner. A 24-hr transcriptome profiling liver identified 37 robustly time independently -associated transcripts potential markers liver. Such genes participated xenobiotic transport, lipid metabolism. We also 10–15% rhythmic control groups, only 4% (1033 genes) were across both conditions – amongst these, several core genes. In-depth rhythm analyses showed that most changes transcript related to mesor (50%), followed amplitude (10%), phase (10%). Gene enrichment analysis revealed state-dependent reorganization metabolic glucose At levels, we observed weakening or loss rhythmicity for associated fatty acid suggesting increased hepatic turnover. summary, provide evidence tonic restructure diurnal independent local molecular clocks.

Язык: Английский

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Nonalcoholic Steatohepatitis Disrupts Diurnal Liver Transcriptome Rhythms in Mice

Cellular and Molecular Gastroenterology and Hepatology, Год журнала: 2023, Номер 16(3), С. 341 - 354

Опубликована: Янв. 1, 2023

Background & AimsThe liver ensures organismal homeostasis through modulation of physiological functions over the course day. How diseases such as nonalcoholic steatohepatitis (NASH) affect daily transcriptome rhythms in remains elusive.MethodsTo start closing this gap, we evaluated impact NASH on diurnal regulation mice. In addition, investigated how stringent consideration circadian rhythmicity affects outcomes analyses.ResultsComparative rhythm analysis from diet-induced and control mice showed an almost 3-hour phase advance global gene expression rhythms. Rhythmically expressed genes associated with DNA repair cell-cycle increased overall amplitude. contrast, lipid glucose metabolism–associated loss amplitude, reduced expression, advances livers. Comparison NASH-induced responses between published studies little overlap (12%) differentially (DEGs). However, by controlling for sampling time using analytical tools, a 7-fold increase DEG detection was achieved compared methods without control.ConclusionsNASH had strong effect phase- amplitude-specific effects key metabolic cell pathways, respectively. Accounting markedly improves enhances reproducibility. The elusive. To analyses. Comparative control.

Язык: Английский

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Melanopsin (Opn4) is an oncogene in cutaneous melanoma

Communications Biology, Год журнала: 2022, Номер 5(1)

Опубликована: Май 13, 2022

Abstract The search for new therapeutical targets cutaneous melanoma and other cancers is an ongoing task. We expanded this knowledge by evaluating whether opsins, light- thermo-sensing proteins, could display tumor-modulatory effects on cancer. Using different experimental approaches, we show that cell proliferation slower in the absence of Opn4 , compared to WT due impaired cycle progression reduced melanocyte inducing transcription factor ( Mitf ) expression. In vivo tumor KO cells remarkably proliferation, higher immune system response tumors. pharmacological assays, demonstrate guanylyl cyclase activity cells. Evaluation Tumor Cancer Genome Atlas (TCGA) database confirms our data as MITF OPN4 expression human correlates with presence microenvironment (TME). Proteomic analyses bulk growth tumors associated signaling, translation G2/M activity. Conversely, increased small GTPase immune-suppressive TME are found. Such evidence points oncogene melanoma, which be pharmacologically targeted.

Язык: Английский

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Step in Time: Conservation of Circadian Clock Genes in Animal Evolution

Integrative and Comparative Biology, Год журнала: 2022, Номер 62(6), С. 1503 - 1518

Опубликована: Сен. 7, 2022

Abstract Over the past few decades, molecular mechanisms responsible for circadian phenotypes of animals have been studied in increasing detail mammals, some insects, and other invertebrates. Particular proteins their interactions are shared across evolutionary distant animals, resulting a hypothesis canonical clock animals. As number species which clockwork has described increases, driving cyclical becomes less similar. Our focus this review is to develop synthesize current literature better understand antiquity evolution animal clockwork. Here, we provide an updated understanding largely through lens conserved genes characterized identified bilaterian species. These comparisons reveal extensive variation within likely composition core mechanism, including losses many genes, that ancestral does not equate clock. Despite loss these retain behaviors physiology, suggesting novel clocks evolved repeatedly. Additionally, highlight highly cellular processes (e.g., cell division, nutrition) intersect with The conservation throughout tree remains essentially unknown, but role maintenance will important areas future study.

Язык: Английский

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Hierarchy or Heterarchy of Mammalian Circadian Timekeepers?

Journal of Biological Rhythms, Год журнала: 2024, Номер unknown

Опубликована: Окт. 24, 2024

Mammalian circadian biologists commonly characterize the relation between clocks as hierarchical, with clock in suprachiasmatic nucleus at top of hierarchy. The lineage research since (SCN) was first identified mammals has challenged this perspective, revealing peripheral tissues, showing that they respond to their own zeitgebers, coordinate oscillations among themselves, and some cases modify behavior SCN. Increasingly timekeepers appear constitute a heterarchical network, control distributed operating along multiple pathways. One reason for continued invocation hierarchy mammalian biology is it difficult understand how system could operate effectively so maintain organism. Evolved mechanisms, however, need not respect those have survived demonstrated ability organizaton organisms.

Язык: Английский

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Back to Roots: Dysbiosis, Obesity, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Obstructive Sleep Apnea—Is There an Objective Connection? A Narrative Review

Nutrients, Год журнала: 2024, Номер 16(23), С. 4057 - 4057

Опубликована: Ноя. 26, 2024

In recent decades, it has become clear that the gut is more than just a digestive organ; also functions as an immune organ with regulatory capabilities and acts “second brain” influences brain function due to presence roles of microbiota (GM). The GM crucial component its host significantly impacts human health. Dysbiosis, or microbial imbalance, been closely linked various diseases, including gastrointestinal, neurological, psychiatric, metabolic disorders. aim this narrative review highlight in maintaining Sleep vital biological necessity, living organisms having evolved internal sleep–wake rhythm aligns roughly 24 h light/dark cycle, known circadian rhythm. This cycle essential for tissue repair, restoration, overall optimal body functioning. irregularities have prevalent modern society, fast-paced lifestyles often disrupting normal sleep patterns. Urban factors, such fast food consumption, shift work, exposure artificial light nighttime noise, medications, social activities, can adversely affect rhythms, dysbiosis being one many factors incriminated etiology

Язык: Английский

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Basic research on circadian disruption using animal and human organoid models: a review

Biological Rhythm Research, Год журнала: 2025, Номер unknown, С. 1 - 22

Опубликована: Фев. 1, 2025

Язык: Английский

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Rhythms in Remodeling: Posttranslational Regulation of Bone by the Circadian Clock

Biomedicines, Год журнала: 2025, Номер 13(3), С. 705 - 705

Опубликована: Март 13, 2025

The circadian clock is a fundamental timekeeping system that regulates rhythmic biological processes in response to environmental light–dark cycles. In mammals, core genes (CLOCK, BMAL1, PER, and CRY) orchestrate these rhythms through transcriptional–translational feedback loops, influencing various physiological functions, including bone remodeling. Bone homeostasis relies on the coordinated activities of osteoblasts, osteoclasts, osteocytes, with increasing evidence highlighting role regulation maintaining skeletal integrity. Disruptions are linked disorders such as osteoporosis. Posttranslational modifications (PTMs), phosphorylation, acetylation, ubiquitination, serve crucial regulators both mechanisms metabolism. However, specific PTMs integrating timing remodeling remains underexplored. This review examines intersection biology, elucidating their impact cell function homeostasis. Understanding interactions may uncover novel therapeutic targets for diseases associated disruptions.

Язык: Английский

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Grape seed procyanidins modulate PER2 circadian rhythm and lipid metabolism of white adipose tissue explants in a time-dependent manner

International Journal of Food Sciences and Nutrition, Год журнала: 2025, Номер unknown, С. 1 - 13

Опубликована: Апрель 29, 2025

The consumption of grape seed procyanidin extract (GSPE) may improve metabolic alterations and molecular clock desynchrony in white adipose tissue (WAT), depending on administration timing status. To test this hypothesis, inguinal WAT explants from lean obese PERIOD2::LUCIFERASE (PER2::LUC) circadian reporter mice were treated at the peak or trough PER2 luminescence rhythm with metabolites present serum GSPE-administered rats (GSPM). PER2::LUC rhythms animals presented a lower amplitude, longer period phase delay. GSPM treatment increased amplitude compared to untreated explants, but only when it was given luminescence. upregulated lipogenesis lipolysis genes mice, mostly peak. This study provides valuable platform for testing effects natural products ex vivo warrants further investigation into chrono-utilisation plant bioactive compounds.

Язык: Английский

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