Acute and long-term exercise adaptation of adipose tissue and skeletal muscle in humans: a matched transcriptomics approach after 8-week training-intervention

International Journal of Obesity, Journal Year: 2023, Volume and Issue: 47(4), P. 313 - 324

Published: Feb. 11, 2023

Exercise exerts many health benefits by directly inducing molecular alterations in physically utilized skeletal muscle. Molecular adaptations of subcutaneous adipose tissue (SCAT) might also contribute to the prevention metabolic diseases.To characterize response human SCAT based on changes transcripts and mitochondrial respiration acute repeated bouts exercise comparison muscle.Sedentary participants (27 ± 4 yrs) with overweight or obesity underwent 8-week supervised endurance 3×1h/week at 80% VO2peak. Before, 60 min after first last bout 5 days post intervention, biopsies were taken for transcriptomic analyses high-resolution respirometry (n = 14, 8 female/6 male).In SCAT, we found 37 acutely regulated (FC > 1.2, FDR < 10%) compared 394, respectively, Regulation only overlapped between tissues highlighting their differential response. Upstream enrichment revealed reduced lipid uptake, storage lipogenesis point β-adrenergic regulation as potential major driver. The data suggest an exercise-induced modulation circadian clock SCAT. Neither term was associated No evidence beigeing/browning along unchanged respiration.Adipose responds completely distinct from muscle exercise. reduction lipogenesis, interconnected a modulated rhythm, can counteract syndrome progression toward diabetes.

Language: Английский

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NAMPT-dependent NAD ⁺ biosynthesis controls circadian metabolism in a tissue-specific manner

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(14)

Published: March 30, 2023

Molecular clocks in the periphery coordinate tissue-specific daily biorhythms by integrating input from hypothalamic master clock and intracellular metabolic signals. One such key signal is cellular concentration of NAD + , which oscillates along with its biosynthetic enzyme, nicotinamide phosphoribosyltransferase (NAMPT). levels feed back into to influence rhythmicity biological functions, yet whether this fine-tuning occurs ubiquitously across cell types a core feature unknown. Here, we show that NAMPT-dependent control over molecular varies substantially between tissues. Brown adipose tissue (BAT) requires NAMPT sustain amplitude clock, whereas white (WAT) only moderately dependent on biosynthesis, skeletal muscle completely refractory loss NAMPT. In BAT WAT, differentially orchestrates oscillation clock-controlled gene networks diurnality metabolite levels. coordinates TCA cycle intermediates BAT, but not abolishes these oscillations similarly high-fat diet-induced circadian disruption. Moreover, depletion improved ability animals defend body temperature during cold stress time-of-day-independent manner. Thus, our findings reveal peripheral are shaped highly manner synthesis.

Language: Английский

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Time of day determines postexercise metabolism in mouse adipose tissue

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(8)

Published: Feb. 13, 2023

The circadian clock is a cell-autonomous transcription–translation feedback mechanism that anticipates and adapts physiology behavior to different phases of the day. A variety factors including hormones, temperature, food-intake, exercise can act on tissue-specific peripheral clocks alter expression genes influence metabolism, all in time-of-day dependent manner. aim this study was elucidate effects timing adipose tissue metabolism. We performed RNA sequencing inguinal mice immediately following maximal or sham treatment at early rest active phase. Only during phase did elicit an immediate increase serum nonesterified fatty acids. Furthermore, increased markers thermogenesis mitochondrial proliferation tissue. In vitro, synchronized 3T3-L1 adipocytes showed timing-dependent difference Adrb2 expression, as well greater lipolytic activity. Thus, response sensitive may be partly driven by clock. To determine feeding state exercise, we replicated experiment 10-h-fasted mimic metabolic status. 10-h fast led similar observed after but not replicate transcriptomic response, suggesting changes gene are conclusion, acute elicits timing-specific maintain homeostasis.

Language: Английский

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Skeletal muscle gene expression dysregulation in long-term spaceflights and aging is clock-dependent

npj Microgravity, Journal Year: 2023, Volume and Issue: 9(1)

Published: April 3, 2023

The circadian clock regulates cellular and molecular processes in mammals across all tissues including skeletal muscle, one of the largest organs human body. Dysregulated rhythms are characteristic aging crewed spaceflight, associated with, for example, musculoskeletal atrophy. Molecular insights into spaceflight-related alterations regulation muscle still missing. Here, we investigated potential functional consequences disruptions on using published omics datasets obtained from spaceflights other clock-altering, external (fasting exercise), or internal (aging) conditions Earth. Our analysis identified network muscle-associated pathways, as a result spaceflight duration mice, which resembles aging-related gene expression changes observed humans Earth (e.g., ATF4 downregulation, with atrophy). Furthermore, according to our results, factors such exercise fasting lead core-clock network, may compensate disruption during spaceflights. Thus, maintaining functioning is crucial ameliorate unphysiological atrophy reported among astronauts.

Language: Английский

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The Cardiac Circadian Clock

JACC Basic to Translational Science, Journal Year: 2023, Volume and Issue: 8(12), P. 1613 - 1628

Published: June 21, 2023

Virtually all aspects of physiology fluctuate with respect to the time day. This is beautifully exemplified by cardiovascular physiology, for which blood pressure and electrophysiology exhibit robust diurnal oscillations. At molecular/biochemical levels (eg, transcription, translation, signaling, metabolism), cardiovascular-relevant tissues (such as heart) are profoundly different during day vs night. Unfortunately, this in turn contributes toward 24-hour rhythms both risk adverse event onset arrhythmias, myocardial infarction) pathogenesis severity extent ischemic damage). Accumulating evidence indicates that cell-autonomous timekeeping mechanisms, termed circadian clocks, temporally govern biological processes known play critical roles function/dysfunction. In paper, a comprehensive review our current understanding cardiomyocyte clock health disease detailed. Unprecedented basic, translational, epidemiologic studies support need implement chronobiological considerations strategies designed prevention treatment disease.

Language: Английский

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