ArticleCritical care (London, England)2021
Altered cholesterol homeostasis in critical illness-induced muscle weakness: effect of exogenous 3-hydroxybutyrate.
Article in Critical care (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- Glucocorticoid treatment increases cholesterol availability during critical illness: effect on adrenal and muscle function.Critical care (London, England) · 2024Trial
- Revisiting hypocholesterolemia during prolonged sepsis: From targeted cholesterol repletion to unresolved adrenal and muscle dysfunction.Molecular and cellular endocrinology · 2026Article
- Cholesterol-depleting dextrin depolarizes sarcolemma: the contribution of sodium / calcium channels and membrane integrity.Pflugers Archiv : European journal of physiology · 2026Article
- Diabetes Management Strategies in Intensive Care Settings.The Medical clinics of North America · 2026Review
- Impact of the Combination of Epigallocatechin Gallate and Ellagic Acid Supplemented with Ketone Bodies on Energetic Restoration of Mitochondrial Dysfunction and Metabolic Inefficiencies in Patients with Multiple Sclerosis: A Review.International journal of molecular sciences · 2026Review
- The impact of lipid-rich nutrition on ketogenesis and muscle weakness in sepsis.Intensive care medicine experimental · 2026Article
- Skeletal Muscle Mass Modifies the Prognostic Impact of LDL Cholesterol in Chronic Heart Failure.Journal of cachexia, sarcopenia and muscle · 2026Article
- The metabolic response to stress in critical illness: updated review on the pathophysiological mechanisms, consequences, and therapeutic implications.Annals of intensive care · 2025Review
- Article
- Sepsis-induced hypocholesterolemia is linked to low cardiomyocyte membrane cholesterol and impaired catecholamine responsiveness.Critical care (London, England) · 2025Observational
- Increased fat accumulation may be associated with severe muscle wasting in critically ill patients: a prospective observational study.Scientific reports · 2025Observational
- On how to feed critically ill children in intensive care: A slowly shifting paradigm.Clinical nutrition (Edinburgh, Scotland) · 2025Review
- Effects of membrane cholesterol-targeting chemicals on skeletal muscle contractions evoked by direct and indirect stimulation.Journal of muscle research and cell motility · 2024Article
- Extracellular Vesicles Modulate Liver Cells Viability and Reactive Oxygen Species in Patients Following a Very Low-Calorie Ketogenic Diet.Nutrients · 2024Article
- [Dietary Management of Obesity].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2024Review
- Ketogenic diet in treating sepsis-related acquired weakness: is it friend or foe?Frontiers in nutrition · 2024Review
- Metabolic Messengers: ketone bodies.Nature metabolism · 2023Review
- Impact of critical illness on cholesterol and fatty acids: insights into pathophysiology and therapeutic targets.Intensive care medicine experimental · 2023Review
- The Impact of a Very-Low-Calorie Ketogenic Diet in the Gut Microbiota Composition in Obesity.Nutrients · 2023Review
- Integration of Transcriptomics and Non-Targeted Metabolomics Reveals the Underlying Mechanism of Skeletal Muscle Development in Duck during Embryonic Stage.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMuscle weakness is a complication of critical illness which hampers recovery. In critically ill mice, supplementation with the ketone body 3-hydroxybutyrate has been shown to improve muscle force and to normalize illness-induced hypocholesterolemia. We hypothesized that altered cholesterol homeostasis is involved in development of critical illness-induced muscle weakness and that this pathway can be affected by 3-hydroxybutyrate.
methodsIn both human critically ill patients and septic mice, the association between circulating cholesterol concentrations and muscle weakness was assessed. In septic mice, the impact of 3-hydroxybutyrate supplementation on cholesterol homeostasis was evaluated with use of tracer technology and through analysis of markers of cholesterol metabolism and downstream pathways.
resultsSerum cholesterol concentrations were lower in weak than in non-weak critically ill patients, and in multivariable analysis adjusting for baseline risk factors, serum cholesterol was inversely correlated with weakness. In septic mice, plasma cholesterol correlated positively with muscle force. In septic mice, exogenous 3-hydroxybutyrate increased plasma cholesterol and altered cholesterol homeostasis, by normalization of plasma mevalonate and elevation of muscular, but not hepatic, expression of cholesterol synthesis genes. In septic mice, tracer technology revealed that 3-hydroxybutyrate was preferentially taken up by muscle and metabolized into cholesterol precursor mevalonate, rather than TCA metabolites. The 3-hydroxybutyrate protection against weakness was not related to ubiquinone or downstream myofiber mitochondrial function, whereas cholesterol content in myofibers was increased.
conclusionsThese findings point to a role for low cholesterol in critical illness-induced muscle weakness and to a protective mechanism-of-action for 3-hydroxybutyrate supplementation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.