Transcriptional programming of lipid and amino acid metabolism by the skeletal muscle circadian clock

PLoS Biology, Journal Year: 2018, Volume and Issue: 16(8), P. e2005886 - e2005886

Published: Aug. 10, 2018

Circadian clocks are fundamental physiological regulators of energy homeostasis, but direct transcriptional targets the muscle clock machinery unknown. To understand how directs rhythmic metabolism, we determined genome-wide binding master brain and ARNT-like protein 1 (BMAL1) REV-ERBα in murine muscles. Integrating occupancy with 24-hr gene expression metabolomics after muscle-specific loss BMAL1 REV-ERBα, here unravel novel molecular mechanisms connecting function to daily cycles lipid metabolism. Validating using luciferase assays vivo rescue, demonstrate a major role is promote diurnal neutral storage while coordinately inhibiting catabolism prior awakening. This occurs by BMAL1-dependent activation Dgat2 REV-ERBα-dependent repression involved metabolism turnover (MuRF-1, Atrogin-1). Accordingly, associated metabolic inefficiency, impaired triglyceride biosynthesis, accumulation bioactive lipids amino acids. Taken together, our data provide comprehensive overview genomic related temporal changes metabolite fluctuations.

Language: Английский

---

Off the Clock: From Circadian Disruption to Metabolic Disease

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(7), P. 1597 - 1597

Published: March 30, 2019

Circadian timekeeping allows appropriate temporal regulation of an organism’s internal metabolism to anticipate and respond recurrent daily changes in the environment. Evidence from animal genetic models humans under circadian misalignment (such as shift work or jet lag) shows that disruption rhythms contributes development obesity metabolic disease. Inappropriate timing food intake high-fat feeding also lead disruptions coordination physiology subsequently promote its pathogenesis. This review illustrates impact genetically environmentally induced molecular clock (at level brain peripheral tissues) interplay between system processes. Here, we discuss some mechanisms responsible for diet-induced desynchrony consider nutritional cues inter-organ communication, with a particular focus on communication organs brain. Finally, relay environmental information by signal-dependent transcription factors adjust gene oscillations. Collectively, better knowledge which function can be compromised will novel preventive therapeutic strategies other disorders arising desynchrony.

Language: Английский

---

Time-restricted feeding restores muscle function in Drosophila models of obesity and circadian-rhythm disruption

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: June 20, 2019

Abstract Pathological obesity can result from genetic predisposition, obesogenic diet, and circadian rhythm disruption. Obesity compromises function of muscle, which accounts for a majority body mass. Behavioral intervention that counteract arising genetic, diet or disruption improve muscle holds untapped potential to combat the epidemic. Here we show Drosophila melanogaster (fruit fly) subject challenges exhibits metabolic disease phenotypes in skeletal muscle; sarcomere disorganization, mitochondrial deformation, upregulation Phospho-AKT level, aberrant intramuscular lipid infiltration, insulin resistance. Imposing time-restricted feeding (TRF) paradigm flies were fed 12 h during day counteracts obesity-induced dysmetabolism improves performance by suppressing fat deposits, aberrations, markers Importantly, TRF was effective even an irregular lighting schedule mimicking shiftwork. Hence, is dietary combating dysfunction multiple causes.

Language: Английский

---

Circadian Rhythms, Disease and Chronotherapy

Journal of Biological Rhythms, Journal Year: 2021, Volume and Issue: 36(6), P. 503 - 531

Published: Sept. 22, 2021

Circadian clocks are biological timing mechanisms that generate 24-h rhythms of physiology and behavior, exemplified by cycles sleep/wake, hormone release, metabolism. The adaptive value is evident when internal body daily environmental mismatched, such as in the case shift work jet lag or even mistimed eating, all which associated with physiological disruption disease. Studies animal human models have also unraveled an important role functional circadian modulating cellular organismal responses to cues (ex., food intake, exercise), pathological insults (e.g. virus parasite infections), medical interventions medication). With growing knowledge molecular underlying pathophysiology, it becoming possible target for disease prevention treatment. In this review, we discuss recent advances research potential therapeutic applications take patient into account treating

Language: Английский

---

Muscle-to-Brain Signaling Via Myokines and Myometabolites

Brain Plasticity, Journal Year: 2022, Volume and Issue: 8(1), P. 43 - 63

Published: Jan. 7, 2022

Skeletal muscle health and function are important determinants of systemic metabolic homeostasis organism-wide responses, including disease outcome. While it is well known that exercise protects the central nervous system (CNS) from aging disease, only recently this has been found to depend on endocrine capacity skeletal muscle. Here, we review muscle-secreted growth factors cytokines (myokines), metabolites (myometabolites), other unconventional signals (e.g. bioactive lipid species, enzymes, exosomes) mediate muscle-brain muscle-retina communication neuroprotection in response associated processes, such as unfolded protein stress. In addition impacting proteostasis, neurogenesis, cognitive functions, signaling influences complex brain-dependent behaviors, depression, sleeping patterns, biosynthesis neurotransmitters. Moreover, myokine adapts feeding behavior meet energy demands Contrary protective myokines induced by pathways, inactivity wasting may derange expression secretion turn compromise CNS function. We propose tailoring muscle-to-CNS modulating myometabolites combat age-related neurodegeneration brain diseases influenced signals.

Language: Английский

---

Sleep, circadian biology and skeletal muscle interactions: Implications for metabolic health

Sleep Medicine Reviews, Journal Year: 2022, Volume and Issue: 66, P. 101700 - 101700

Published: Oct. 9, 2022

There currently exists a modern epidemic of sleep loss, triggered by the changing demands our 21st century lifestyle that embrace 'round-the-clock' remote working hours, access to energy-dense food, prolonged periods inactivity, and on-line social activities. Disturbances patterns impart widespread adverse effects on numerous cells, tissues, organs. Insufficient causes circadian misalignment in humans, including perturbed peripheral clocks, leading disrupted skeletal muscle liver metabolism, whole-body energy homeostasis. Fragmented or insufficient also perturbs hormonal milieu, shifting it towards catabolic state, resulting reduced rates protein synthesis. The interaction between metabolic health is complex, with mechanisms underpinning sleep-related disturbances this tissue often multifaceted. Strategies promote sufficient duration combined appropriate timing meals physical activity maintain rhythmicity are important mitigate inadequate health. This review summarises complex relationship sleep, biology, muscle, discusses effectiveness several strategies negative disturbed rhythms

Language: Английский

---

Liver and muscle circadian clocks cooperate to support glucose tolerance in mice

Cell Reports, Journal Year: 2023, Volume and Issue: 42(6), P. 112588 - 112588

Published: June 1, 2023

Physiology is regulated by interconnected cell and tissue circadian clocks. Disruption of the rhythms generated concerted activity these clocks associated with metabolic disease. Here we tested interactions between in two critical components organismal metabolism, liver skeletal muscle, rescuing clock function either each organ separately or both organs simultaneously otherwise clock-less mice. Experiments showed that individual are partially sufficient for glucose yet connections coupled to daily feeding support systemic tolerance. This synergy relies part on local transcriptional control machinery, feeding-responsive signals such as insulin, cycles connect muscle liver. We posit spatiotemporal mechanisms play an essential role maintenance homeostasis disrupting this diurnal coordination can contribute

Language: Английский

---

Ecdysone acts through cortex glia to regulate sleep in Drosophila

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 31, 2023

Steroid hormones are attractive candidates for transmitting long-range signals to affect behavior. These lipid-soluble molecules derived from dietary cholesterol easily penetrate the brain and act through nuclear hormone receptors (NHRs) that function as transcription factors. To determine extent which NHRs sleep:wake cycles, we knocked down each of 18 highly conserved found in Drosophila adults report ecdysone receptor (EcR) its direct downstream NHR Eip75B (E75) glia regulate rhythm amount sleep. Given synthesis genes have little no expression fly brain, appears a long-distance signal our data suggest it enters more at night. Anti-EcR staining localizes cortex functional screening glial subtypes revealed EcR functions adult Cortex implicated lipid metabolism, be relevant actions treatment mobilizes droplets (LDs), knockdown results LDs. In addition, sleep-promoting effects exogenous diminished lsd-2 mutant flies, lean deficient accumulation. We propose is systemic secreted factor modulates sleep by stimulating metabolism glia.

Language: Английский

---

Cell state dependent effects of Bmal1 on melanoma immunity and tumorigenicity

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 20, 2024

Language: Английский

---

Decoding the nexus: branched-chain amino acids and their connection with sleep, circadian rhythms, and cardiometabolic health

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(5), P. 1350 - 1363

Published: June 3, 2024

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and, either directly or indirectly, overall body health, encompassing metabolic and cardiovascular well-being. Given the heightened activity of brain, there exists a considerable demand nutrients in comparison to other organs. Among these, branched-chain amino acids, comprising leucine, isoleucine, valine, display distinctive significance, from their contribution protein structure involvement metabolism, especially cerebral processes. first acids that are released into circulation post-food intake, assume pivotal role regulation synthesis, modulating insulin secretion acid sensing pathway target rapamycin. Branched-chain key players influencing brain’s uptake monoamine precursors, competing shared transporter. Beyond these contribute cycles γ-aminobutyric glutamate, well energy metabolism. Notably, they impact GABAergic neurons excitation/inhibition balance. rhythmicity plasma concentrations, observed over 24-hour conserved rodent models, is under circadian clock control. mechanisms underlying those rhythms physiological consequences disruption not fully understood. Disturbed sleep, obesity, diabetes, diseases can elevate concentrations modify oscillatory dynamics. driving effects currently focal point ongoing research efforts, since normalizing levels has ability alleviate severity pathologies. In this context, Drosophila model, though underutilized, holds promise shedding new light on mechanisms. Initial findings indicate its potential introduce novel concepts, particularly elucidating intricate connections between clock, sleep/wake, Consequently, use transport emerge critical components orchestrators web interactions across multiple organs throughout sleep/wake cycle. They could represent one so far elusive connecting sleep patterns paving way therapeutic interventions.

Language: Английский

---