Humans have, throughout history, faced periods of starvation necessitating increased physical effort to gather food. To explore adaptations in muscle function, 13 participants (7 males and 6 females) fasted for seven days. They lost 4.6 ± 0.3 kg lean and 1.4 ± 0.1 kg fat mass. Maximal isometric and isokinetic strength remained unchanged, while peak oxygen uptake decreased by 13%. Muscle glycogen was halved, while expression of electron transport chain proteins was unchanged. Pyruvate dehydrogenase kinase 4 (PDK4) expression increased 13-fold, accompanied by inhibitory pyruvate dehydrogenase phosphorylation, reduced carbohydrate oxidation and decreased exercise endurance capacity. Fasting had no impact on 5' AMP-activated protein kinase (AMPK) activity, challenging its proposed role in muscle protein degradation. The participants maintained muscle strength and oxidative enzymes in skeletal muscle during fasting but carbohydrate oxidation and high-intensity endurance capacity were reduced.
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http://dx.doi.org/10.1038/s41467-024-55418-0 | DOI Listing |
Curr Med Chem
January 2025
Transplant Research Center, Clinical Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Nonalcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disorders following liver transplantation. The prorenin receptor (PRR) plays a role in glucose and lipid metabolism, and the hepatic dysregulation of PRR is associated with the upregulation of several molecular pathways, such as the mammalian target of rapamycin (mTOR) and Peroxisome proliferator-activated receptor (PPAR) that promotes hepatic lipogenesis and leads to lipid accumulation in hepatocytes by upregulation of lipogenic genes. PRR inhibition leads to a reduction in the hepatic expression of sortilin-1 and low-density lipoprotein receptor (LDLR) levels and down-regulation of pyruvate dehydrogenase (PDH) and acetyl-CoA carboxylase (ACC) and reduces fatty acids synthesis in hepatocytes.
View Article and Find Full Text PDFNat Metab
January 2025
CIRI, Centre International de Recherche en Infectiologie, (Team Lyacts), Univ Lyon, INSERM, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.
Resting natural killer (NK) cells display immediate effector functions after recognizing transformed or infected cells. The environmental nutrients and metabolic requirements to sustain these functions are not fully understood. Here, we show that NK cells rely on the use of extracellular pyruvate to support effector functions, signal transduction and cell viability.
View Article and Find Full Text PDFHumans have, throughout history, faced periods of starvation necessitating increased physical effort to gather food. To explore adaptations in muscle function, 13 participants (7 males and 6 females) fasted for seven days. They lost 4.
View Article and Find Full Text PDFNat Commun
January 2025
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Univ. Montpellier, Institut régional du Cancer de Montpellier (ICM), Montpellier, France.
Pyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that plays an essential role during brain development. Using genetically engineered mouse model and primary neuronal cells, we identify the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U).
View Article and Find Full Text PDFJ Environ Manage
December 2024
College of Engineering (Key Laboratory for Clean Renewable Energy Utilization Technology, Ministry of Agriculture), China Agricultural University, Beijing 100083, PR China. Electronic address:
Acidogenic fermentation was an effective technology to recover volatile fatty acids (VFAs) ethanol and lactic acid from food wastes (FW) as bioresources. However, the impact of process controls on key functional enzymes and metabolic pathways has been inadequately understood. In this study, the metabolite distribution, key functional enzymes and metabolic pathways were completely elucidated using 16S rRNA gene high-throughput sequencing combined with PICRUSt2.
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