Cited by 1,460Diet and metabolism studiesLipid metabolism and biosynthesisLipid metabolism and disorders

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Regulation of Hepatic Fatty Acid Oxidation and Ketone Body Production

McGarry, J D, Foster, D W·1980·Annual Review of Biochemistry

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The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More

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Crossref · 10.1146/annurev.bi.49.070180.002143

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“Since NEFA are used by the liver as a principal fuel for hepatic ketogenesis [29,42,43], the efficient reduction in plasma NEFA would contribute to the observed reduction in hyperketonemia.”
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Different sites of inhibition of carnitine palmitoyltransferase by malonyl-CoA, and by acetyl-CoA and CoA, in human skeletal muscle
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Lipid transport function is the main target of oral oleoylethanolamide to reduce adiposity in high-fat-fed mice
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“The transport of fatty acids into the mitochondria is primarily controlled at the level of carnitine palmitoyl transferase-1 (CPT-1) (20).”
Background
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HAMILTON, C., & SAGGERSON, E. D. (2000) · Biochemical Journal · doi:10.1042/bj3500061 · Cited by 44
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Yonetani-Theorell analysis of hepatic carnitine palmitoyltransferase-I inhibition indicates two distinct inhibitory binding sites.
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Interaction of malonyl-CoA and 2-tetradecylglycidyl-CoA with mitochondrial carnitine palmitoyltransferase I.
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“The present results could, at least partially, explain the previous observations of others, who found that within the hepatocyte NA promotes -oxidation of non-esterified fatty acids to ketone bodies.(14) Those who reported(13) decreased acetoacetate (but not -hydroxybutyrate, whose tissue concentration was increased)…”
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“CPT-1 catalyzes the rate-limiting step in mitochondrial FAO (McGarry & Foster, 1980).”
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Evidence for an impaired long‐chain fatty acid oxidation and ketogenesis in Fao hepatoma cells
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“Additionally, MCT intake also increases the energy source by the rapid formation of ketone bodies, because an excess of acetylCoA is produced by metabolizing MCFAs in the liver (4, 6).”
Background
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“Carbohydrates’ catabolism produces a high level of glucose and insulin and is associated with hepatic-free fatty acid (FFA) synthesis [21,35,36].”
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Malonyl-CoA-independent Acute Control of Hepatic Carnitine Palmitoyltransferase I Activity
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Systemic Carnitine Deficiency
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Citrus ichangensisPeel Extract Exhibits Anti-Metabolic Disorder Effects by the Inhibition of PPAR γ and LXR Signaling in High-Fat Diet-Induced C57BL/6 Mouse
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“The liver, one of the insulin-sensitive tissues, plays a pivotal role in the processes of hyperglycemia and dyslipidemia [38, 39].”
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Oxidation of fatty acids in eukaryotes
Schulz, H. (2008) · Elsevier eBooks · doi:10.1016/b978-044453219-0.50007-6 · Cited by 43
Determination of ketone bodies in biological samples via rapid UPLC-MS/MS
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“The generation of ketone bodies is driven through an inter-organ shuttle that initiates with adipose tissue lipolysis of triacylglycerol to free fatty acids, which are transported to the liver for mitochondrial β-oxidation [11].”
Background
Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation
Zhang, X., Gao, T., Deng, S., Shang, L., Chen, X., Chen, K., Li, P., Cui, X., & Zeng, J. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100622 · Cited by 42
“The regulation of ketogenesis by carbohydrate has been established, and malonyl-CoA was identified to be the molecule responsible for the inhibition of carnitine palmitoyltransferase-1a (CPT1a), the critical enzyme in the transfer of long-chain fatty acids into mitochondria, thereby inhibiting ketogenesis and stimulat…”
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Pathophysiology of ketoacidosis in Type 2 diabetes mellitus
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Interactions Between Gluconeogenesis and Fatty Acid Oxidation in Isolated Sheep Hepatocytes
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Hepatic carnitine palmitoyltransferase-I has two independent inhibitory binding sites for regulation of fatty acid oxidation
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Two novel gene mutations (Glu174→Lys, Phe383→Tyr) causing the "hepatic" form of carnitine palmitoyltransferase II deficiency
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“In addition, ketones are of low concentration in plasma under physiological conditions [16]; however, after overnight fasting, ketones provide 10–20% of the overall energy supply, providing a compensatory source of energy in nutritionally deficient states such as HF, ketosis, and fasting/starvation [17,18].”
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Interleukin-6, but not tumour necrosis factor-α, increases lipogenesis in rat hepatocyte primary cultures
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Citrange Fruit Extracts Alleviate Obesity-Associated Metabolic Disorder in High-Fat Diet-Induced Obese C57BL/6 Mouse
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“The liver which is sensitive to insulin plays an important role in glucose and lipid metabolism [43,44].”
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Human ketone body production and utilization studied using tracer techniques: Regulation by free fatty acids, insulin, catecholamines, and thyroid hormones
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“The fact that glucagon inhibits hepatic triglyceride synthesis and enhances b-oxidation may raise the possibility that glucagon is protective against hepatic steatosis (15).”
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Exercise-Induced Autophagy in Fatty Liver Disease
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“ACC1 is responsible for the rate limiting initiation of de novo fatty acid synthesis while ACC2 serves as a negative regulator of fatty acid uptake by the mitochondria via inhibiting carnitine palmitoyltransferase I (CPT1)(And & Foster, 1980).”
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Postoperative serum metabolites of patients on a low carbohydrate ketogenic diet after pancreatectomy for pancreatobiliary cancer: a nontargeted metabolomics pilot study
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“One possibility is that a decrease in fatty acids arriving at the liver had decreased acetyl-CoA for mevalonate synthesis (43).”
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Authors: McGarry, J. D., & Foster, D. W.
ORCID: McGarry, J D
Venue: Annual Review of Biochemistry
Publisher: Annual Reviews
Published: 1980-06
Volume: 49
Issue: 1
Pages: 395-420
ISSN: 0066-4154 (ISSN-L)
1545-4509
DOI: 10.1146/annurev.bi.49.070180.002143
OpenAlex: W2178164598
Cited by: 1,460
References: 0
Citations by year: 2026: 14 · 2025: 28 · 2024: 30 · 2023: 41 · 2022: 39 · 2021: 25 · 2020: 42 · 2019: 47 · 2018: 26 · 2017: 27 · 2016: 33 · 2015: 28 · 2014: 36 · 2013: 35 · 2012: 24
FWCI: 47.01
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Biochemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: hepatic fatty acid oxidation, ketone synthesis, Hippo signaling pathway, hepatic metabolism, tissue growth regulation, organ size control, cell fate determination
MeSH terms: Acetyl Coenzyme A, Adipose Tissue, Animals, Carnitine, Carnitine Acyltransferases, Fatty Acids, Fatty Acids, Nonesterified, Glucagon, Glycogen, Insulin, Ketone Bodies, Liver, Malonyl Coenzyme A, Models, Biological, Triglycerides, Meglutol

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Regulation of Hepatic Fatty Acid Oxidation and Ketone Body Production

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