Ketone bodies are energy substrates produced by the liver during prolonged fasting or low-carbohydrate diet. The ingestion of a ketone ester (KE) rapidly increases blood ketone levels independent of nutritional status. KE has recently been shown to improve exercise performance, but whether it can also promote post-exercise muscle protein or glycogen synthesis is unknown. Eight healthy trained males participated in a randomized double-blind placebo-controlled crossover study. In each session, subjects undertook a bout of intense one-leg glycogen-depleting exercise followed by a 5-h recovery period during which they ingested a protein/carbohydrate mixture. Additionally, subjects ingested a ketone ester (KE) or an isocaloric placebo (PL). KE intake did not affect muscle glycogen resynthesis, but more rapidly lowered post-exercise AMPK phosphorylation and resulted in higher mTORC1 activation, as evidenced by the higher phosphorylation of its main downstream targets S6K1 and 4E-BP1. As enhanced mTORC1 activation following KE suggests higher protein synthesis rates, we used myogenic CC cells to further confirm that ketone bodies increase both leucine-mediated mTORC1 activation and protein synthesis in muscle cells. Our results indicate that adding KE to a standard post-exercise recovery beverage enhances the post-exercise activation of mTORC1 but does not affect muscle glycogen resynthesis in young healthy volunteers. , we confirmed that ketone bodies potentiate the increase in mTORC1 activation and protein synthesis in leucine-stimulated myotubes. Whether, chronic oral KE intake during recovery from exercise can facilitate training-induced muscular adaptation and remodeling need to be further investigated.
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http://dx.doi.org/10.3389/fphys.2017.00310 | DOI Listing |
Mol Biol Cell
January 2025
Department of Cell Biology, Emory University, 615 Michael St, Atlanta, GA, USA, 30322.
Rare inherited diseases caused by mutations in the copper transporters (CTR1) or induce copper deficiency in the brain, causing seizures and neurodegeneration in infancy through poorly understood mechanisms. Here, we used multiple model systems to characterize the molecular mechanisms by which neuronal cells respond to copper deficiency. Targeted deletion of CTR1 in neuroblastoma cells produced copper deficiency that produced a metabolic shift favoring glycolysis over oxidative phosphorylation.
View Article and Find Full Text PDFHum Mol Genet
January 2025
Department of Cell & Developmental Biology, Vanderbilt University School of Medicine, 1161 21st Ave S, Nashville, Tennessee, 37232, United States of America.
Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. While benign tumors in the heart, lungs, kidney, and brain are all hallmarks of the disease, the most severe symptoms of TSC are often neurological, including seizures, autism, psychiatric disorders, and intellectual disabilities. TSC is caused by loss of function mutations in the TSC1 or TSC2 genes and consequent dysregulation of signaling via mechanistic Target of Rapamycin Complex 1 (mTORC1).
View Article and Find Full Text PDFJ Am Soc Nephrol
January 2025
Nephrology Division, Department of Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Background: Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis (PD) and abdominal surgeries, yet effective treatments remain elusive. Given the known roles of mucosal-associated invariant T (MAIT) cells in immune responses and fibrotic diseases, we investigated their involvement in PD-induced peritoneal fibrosis to identify potential therapeutic targets.
Methods: We employed single-cell RNA sequencing (scRNA-seq) and flow cytometry to characterize the activation and function of peritoneal MAIT cells in patients undergoing long-term PD.
Life Med
June 2024
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education) of the Second Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310029, China.
SHOC2 is a scaffold protein that activates the RAS-MAPK signal. Our recent study showed that SHOC2 is also a negative regulator of the mTORC1 signal in lung cancer cells. Whether and how SHOC2 differentially regulates the RAS-MAPK vs.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
January 2025
Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, IL, USA.
Hepatic lipotoxicity, resulting from excessive lipid accumulation in hepatocytes, plays a central role in the pathogenesis of various metabolic liver diseases. Despite recent progress, the precise mechanisms remain incompletely understood. Employing excessive exposure to palmitate in hepatocytes as our primary experimental model and mice studies, we aimed to uncover the mechanisms behind hepatic lipotoxicity, thereby developing potential treatments.
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