ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Branched chain amino acids and carbohydrate restriction exacerbate ketogenesis and hepatic mitochondrial oxidative dysfunction during NAFLD.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Gut Mycobiota-Associated Tryptophan Catabolites Protect Against Metabolic Dysfunction-Associated Steatotic Liver Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rewiring Adipocyte Plasticity: The Redox-Mitochondrial Axis as a Driver of Beige Fat Immunometabolism and Adipose Inflammation.Biomolecules · 2026Review
- Plasma metabolomic signatures in children with autism spectrum disorder and their modulation following a gluten-free modified ketogenic diet.BMC psychiatry · 2026Article
- Gut microbiome composition and metabolic activity in metabolic-associated fatty liver disease.Virulence · 2025Article
- Review
- Targeted metabolomics reveals bioactive inflammatory mediators from gut into blood circulation in children with NAFLD.NPJ biofilms and microbiomes · 2025Article
- Gut microbiota in non-alcoholic fatty liver disease: Pathophysiology, diagnosis, and therapeutics.World journal of hepatology · 2025Review
- Induction of Fructose Mediated De Novo Lipogenesis Coexists with the Upregulation of Mitochondrial Oxidative Function in Mice Livers.The Journal of nutrition · 2025Article
- Clinical characteristics of lean and non-lean non-alcoholic fatty liver disease: a cross-sectional study.Nutrition & metabolism · 2025Article
- Advancing Obesity Management: the Very Low-Energy Ketogenic therapy (VLEKT) as an Evolution of the "Traditional" Ketogenic Diet.Current obesity reports · 2025Review
- Detecting altered hepatic lipid oxidation by MRI in an animal model of MASLD.Cell reports. Medicine · 2024Article
- Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis.Open life sciences · 2024Article
- Branched-chain amino acids alter cellular redox to induce lipid oxidation and reduce de novo lipogenesis in the liver.American journal of physiology. Endocrinology and metabolism · 2023Article
- Oxymatrine Alleviates High-Fat-High-Fructose-Induced Fatty Liver in Rats: Understanding the Molecular Mechanism Through an Untargeted Metabonomics Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- The Emerging Role of Branched-Chain Amino Acids in Liver Diseases.Biomedicines · 2022Review
- INCA 2.0: A tool for integrated, dynamic modeling of NMR- and MS-based isotopomer measurements and rigorous metabolic flux analysis.Metabolic engineering · 2022Article
- Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD).Frontiers in endocrinology · 2022Review
- Coordinated pyruvate kinase activity is crucial for metabolic adaptation and cell survival during mitochondrial dysfunction.Human molecular genetics · 2021Article
- In vivoCurrent opinion in biotechnology · 2021Review
- Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondrial adaptation during non-alcoholic fatty liver disease (NAFLD) include remodeling of ketogenic flux and sustained tricarboxylic acid (TCA) cycle activity, which are concurrent to onset of oxidative stress. Over 70% of obese humans have NAFLD and ketogenic diets are common weight loss strategies. However, the effectiveness of ketogenic diets toward alleviating NAFLD remains unclear. We hypothesized that chronic ketogenesis will worsen metabolic dysfunction and oxidative stress during NAFLD. Mice (C57BL/6) were kept (for 16-wks) on either a low-fat, high-fat, or high-fat diet supplemented with 1.5X branched chain amino acids (BCAAs) by replacing carbohydrate calories (ketogenic). The ketogenic diet induced hepatic lipid oxidation and ketogenesis, and produced multifaceted changes in flux through the individual steps of the TCA cycle. Higher rates of hepatic oxidative fluxes fueled by the ketogenic diet paralleled lower rates of de novo lipogenesis. Interestingly, this metabolic remodeling did not improve insulin resistance, but induced fibrogenic genes and inflammation in the liver. Under a chronic "ketogenic environment," the hepatocyte diverted more acetyl-CoA away from lipogenesis toward ketogenesis and TCA cycle, a milieu which can hasten oxidative stress and inflammation. In summary, chronic exposure to ketogenic environment during obesity and NAFLD has the potential to aggravate hepatic mitochondrial dysfunction.
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