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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Abstract

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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“The resultant excess acetyl-CoA, along with depleted oxaloacetate, is diverted toward excessive KB production, leading to the release of substantial quantities of β -HB and acetoacetate into the blood [81,82].”
PLAAT1 deficiency alleviates high‐fat diet‐induced hepatic lipid accumulation in mice
Rahman, S., Sasaki, S., Uyama, T., Hussain, Z., Sikder, M. M., Saiga, H., Ohmura‐Hoshino, M., Ohta, K., Miki, Y., Hoshino, K., et al. (2023) · The FASEB Journal · doi:10.1096/fj.202201033r · Cited by 15
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Background
Alcohol-induced ketonemia is associated with lowering of blood glucose, downregulation of gluconeogenic genes, and depletion of hepatic glycogen in type 2 diabetic db/db mice
Srinivasan, M. P., Shawky, N. M., Kaphalia, B. S., et al. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.12.005 · Cited by 14
“Increased systemic levels of βOHB are primarily attributed to enhanced hepatic ketogenesis, which occurs when acetyl-CoA generated through β-oxidation of fatty acids exceeds cellular energy requirements [10,11].”
Acute fructose intake suppresses fasting-induced hepatic gluconeogenesis through the AKT-FoxO1 pathway
Sato, T., Watanabe, Y., Nishimura, Y., Inoue, M., Morita, A., & Miura, S. (2019) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2019.100638 · Cited by 14
“Insulin also suppresses β-oxidation and the concentration of blood ketone bodies in the liver [25].”
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A new strategy to alleviate the obesity induced by endocrine disruptors—A unique lysine metabolic pathway of nanoselenium Siraitia grosvenorii to repair gut microbiota and resist obesity
Wang, Y., Sun, W., Yan, S., Meng, Z., Jia, M., Tian, S., Huang, S., Sun, X., Han, S., Pan, C., et al. (2023) · Food and Chemical Toxicology · doi:10.1016/j.fct.2023.113737 · Cited by 14
TNF‐α and IL‐6 Synergistically Inhibit Ketogenesis From Fatty Acids and α‐Ketoisocaproate in Isolated Rat Hepatocytes
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Maturation of fatty acid and carbohydrate metabolism in the newborn heart
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Response to acute nickel toxicity in rats as a function of sex
Alc�n, M. P., Arola, L., & Mas, A. (1991) · BioMetals · doi:10.1007/bf01141303 · Cited by 14
“However, it is well known that the hyperglycemic effect of glucagon in vivo is rapidly reduced by a subsequent release of insulin, since the hyperglycemia is a result of hormone imbalance (McGarry and Foster 1980).”
Background
Regulation of hepatic triacylglycerol synthesis and secretion
Haagsman, H. P., & GOLDE, L. M. G. V. (1984) · Veterinary Research Communications · doi:10.1007/bf02214708 · Cited by 13
“More attractive is the hypothesis that malonyl-CoA is an important regulatory factor in determining the control of hepatic fatty acid oxidation (MeGarry and Foster, 1980).”
Background
Lipase-catalysed resolution of N-(3-cyano-2-hydroxy propan-1-yl)phthalimide
Kamal, Ä., Tadiparthi, K., & Khan, M. N. A. (2007) · Journal of Molecular Catalysis B Enzymatic · doi:10.1016/j.molcatb.2007.03.002 · Cited by 14
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Effects of Chronic Ethanol Exposure on Cardiac Receptor‐Adenylyl Cyclase Coupling: Studies in Cultured Embryonic Chick Myocytes and Ethanol Fed Rats
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Effects of volatile fatty acids and ketone bodies on lipolysis in isolated adipocytes from Norwegian reindeer (Rangifer tarandus)
Larsen, T. S., Nilsson, N. Ö., & Blix, A. S. (1983) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1983.tb00020.x · Cited by 14
Fifth Annual Jonathan E. Rhoads Lecture. Metabolic Integration of Organs in Health and Disease
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Effect of feeding pattern on the sensitivity of hepatic carnitine palmitoyl-transferase to inhibition by malonyl-CoA in the rat
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Temperature dependence of lipogenesis in isolated hepatocytes from rainbow trout (Salmo gairdneri)
Voß, B., Jankowsky, H.-D., & Weddigen, P. (1986) · Comparative Biochemistry and Physiology Part B Comparative Biochemistry · doi:10.1016/0305-0491(86)90325-1 · Cited by 14
Alterations in the Regulatory Properties of Hepatic Fatty Acid Oxidation and Carnitine Palmitoyltransferase I Activity after Ethanol Feeding and Withdrawal
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Impaired ketogenesis in patients with adult-type citrullinemia
Inui, Y., Kuwajima, M., Kawata, S., et al. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90241-0 · Cited by 14
Expression of precursor and mature carnitine palmitoyltransferase II in Escherichia coli and in vitro: differential behaviour of rat and human isoforms
Brown, N. F., Sen, A., Soltis, D. A., Jones, B., Foster, D. W., & McGarry, J. (1993) · Biochemical Journal · doi:10.1042/bj2940079 · Cited by 14
Self-citation
Fatty Acid Metabolism in the Heart Following Diabetes
Lopaschuk, G. D. (1996) · Developments in cardiovascular medicine · doi:10.1007/978-1-4613-1269-7_10 · Cited by 13
Total Parenteral Nutrition Containing Medium- vs. Long-Chain Triglyceride Emulsions Elevates Plasma Cholesterol Concentrations in Rats , ,
Ney, D. M., Yang, H. M., Rivera, J., et al. (1993) · Journal of Nutrition · doi:10.1093/jn/123.5.883 · Cited by 14
Disordered expression of glycolytic and gluconeogenic liver enzymes of juvenile visceral steatosis mice with systemic carnitine deficiency
Hotta, K., Kuwajima, M., Ono, A., Nakajima, H., Horikawa, Y., Miyagawa, J.-I., Namba, M., Hanafusa, T., Horiuchi, M., Nikaido, H., et al. (1996) · Diabetes Research and Clinical Practice · doi:10.1016/0168-8227(96)01247-8 · Cited by 14
Targeting ketone body metabolism to treat fatty liver disease
Kwon, S., Jeyaratnam, R., & Kim, K.-H. (2024) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.3389/jpps.2024.13375 · Cited by 17
“AcAc is then further converted to BHB by β -hydroxybutyrate dehydrogenase (BDH1) [24 – 26].”
Background
Potential of trace elements as supplements for the metabolic control of Type 2 Diabetes Mellitus: A systematic review
Moreira, L. D. P. D., Gomes, J. V., Mattar, J. B., Chaves, L. F., & Martino, H. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.04.015 · Cited by 13
Hepatokines, bile acids and ketone bodies are novel Hormones regulating energy homeostasis
Garruti, G., Baj, J., Cignarelli, A., Perrini, S., & Giorgino, F. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1154561 · Cited by 15
“support of the insulin–resistant role of Fetuin–B, there are also animal studies showing that mice treated with Fetuin–B develop impaired glucose tolerance (31).”
BackgroundResult
Impaired Glucose Tolerance is Characterized by Multiple Abnormalities in the Regulation of Intermediary Metabolism
Krentz, A., Singh, B. M., & Nattrass, M. (1991) · Diabetic Medicine · doi:10.1111/j.1464-5491.1991.tb02123.x · Cited by 13
Brain substrates and the effects of nutrition
Williamson, D. H. (1987) · Proceedings of The Nutrition Society · doi:10.1079/pns19870011 · Cited by 13
Effects of Neutral Detergent Fiber from Rice Straw on Blood Metabolites and Productivity of Dairy Cows in the Tropics Center.
Kanjanapruthipong, J., & Thaboot, B. (2006) · Asian-Australasian Journal of Animal Sciences · doi:10.5713/ajas.2006.356 · Cited by 13
Comparative Serum Fatty Acid Profiles of Captive and Free-Ranging Cheetahs (Acinonyx jubatus) in Namibia
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Distinct Roles for Brain and Pancreas in Basal and Postprandial Glucose Homeostasis
Alonge, K. M., Porte, D., & Schwartz, M. W. (2023) · Diabetes · doi:10.2337/db22-0969 · Cited by 13
Octanoate metabolism in isolated hepatocytes and mitochondria from fetal, newborn and adult rabbit
Pégorier, J. P., Duée, P., Clouet, P., Kohl, C., Herbin, C., & Girard, J. R. (1989) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1989.tb15067.x · Cited by 13
Effects of streptozotocin-induced diabetes on acetoacetyl-CoA synthetase activity in rats
Sato, H., Takahashi, N. K., Nakamoto, M., et al. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)00911-5 · Cited by 13
Physical training reverses the increased activity of the hepatic ketone body synthesis pathway in chronically diabetic rats
Midaoui, A. E., Chiasson, J., Tancrède, G., & Nadeau, A. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00608.2004 · Cited by 13
“Ketone bodies are synthesized in liver mitochondria by a four-step enzymatic pathway that involves acetoacetyl-CoA thiolase, 3-hydroxy-3methylglutaryl-CoA (HMG-CoA) synthase, hydroxymethylglutaryl-CoA lyase, and 3-hydroxybutyrate dehydrogenase (13).”
Background
Malonic aciduria in Maltese dogs: Normal methylmalonic acid concentrations and malonyl‐CoA decarboxylase activity in fibroblasts
O’Brien, D. P., Barshop, B. A., Faunt, K. K., et al. (1999) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005635306257 · Cited by 13
“During the fasting state, malonyl-CoA levels decrease, allowing free fatty acids to be transported into the mitochondria for b-oxidation (McGarry and Foster 1980).”
BackgroundInfluential
Rat hepatic microsomal acetoacetyl-CoA reductase. A beta-ketoacyl-CoA reductase distinct from the long chain beta-ketoacyl-CoA reductase component of the microsomal fatty acid chain elongation system.
Prasad, M. R., Cook, L., Vieth, R., & Cinti, D. L. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42813-4 · Cited by 13
Over-expression and characterization of active recombinant rat liver carnitine palmitoyltransferase II using baculovirus
Johnson, T. M., Mann, W., Dragland, C. J., Anderson, R. C., Nemecek, G. M., & Bell, P. A. (1995) · Biochemical Journal · doi:10.1042/bj3090689 · Cited by 12
Adipose tissue and liver lipid metabolism in obese children: role of the body mass index and the presence of acanthosis nigricans
Bonet, B., Viana, M., Sánchez‐Vera, I., Quintanar, A., Martínez, J., & Espino, M. (2007) · Diabetic Medicine · doi:10.1111/j.1464-5491.2007.02230.x · Cited by 13
α1-Adrenergic stimulation of ketogenesis and fatty acid oxidation is associated with inhibition of lipogenesis in rat hepatocytes
Stark, B. R., & Keller, U. B. (1987) · Cellular and Molecular Life Sciences · doi:10.1007/bf01956049 · Cited by 13
Expression and Regulation of Carnitine Palmitoyltransferase-lα and -1β Genes
Cook, G. A., & Park, E. A. (1999) · The American Journal of the Medical Sciences · doi:10.1016/s0002-9629(15)40571-3 · Cited by 13
Diabetic ketoacidosis
Bergenstal, R. M. (1985) · Postgraduate Medicine · doi:10.1080/00325481.1985.11698880 · Cited by 12
The action of vasopressin and calcium on palmitate metabolism in hepatocytes and isolated mitochondria from rat liver
Almås, I., Singh, B., & Borrebæk, B. (1983) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(83)90533-7 · Cited by 13
A 6-hour nocturnal interruption of a continuous subcutaneous insulin infusion: 2. Marked attenuation of the metabolic deterioration by somatostatin
Scheen, A. J., Krzentowski, G., Castillo, M. J., Lef�bvre, P. J., & LUYCKX, A. S. (1983) · Diabetologia · doi:10.1007/bf00251816 · Cited by 13
“This view is in agreement with the current theory on the role of glucagon in ketogenesis as recently reviewed by McGarry and Foster [ 23 ].”
Result
Studies on the mechanism of action of the hypoglycemic agent, 2-(3-methylcinnamylhydraznoo)-propionate (BM 42.304)
Deaciuc, I. V., Kühnle, H. F., Strauss, K., et al. (1983) · Biochemical Pharmacology · doi:10.1016/0006-2952(83)90369-6 · Cited by 13
Therapeutic Potential of Peroxisome Proliferator-Activated Receptor Modulation in Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis
Gellrich, L., & Merk, D. (2017) · Nuclear Receptor Research · doi:10.11131/2017/101310 · Cited by 13
“Imbalance of fatty acid metabolism can arise from mitochondrial dysfunction leading to increased levels of malonyl-CoA [55].”
Background
A mini review of small-molecule inhibitors targeting palmitoyltransferases
Hu, X., Zhu, X., Yu, W., Zhang, Y., Yang, K., Liu, Z., Qiao, X., & Song, Y. (2022) · European Journal of Medicinal Chemistry Reports · doi:10.1016/j.ejmcr.2022.100041 · Cited by 12
Low-Carbohydrate Ketogenic Diet for Improvement of Glycemic Control: Mechanism of Action of Ketosis and Beneficial Effects
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MRI proton density fat fraction for estimation of tumor grade in steatotic hepatocellular carcinoma
Kupczyk, P. A., Kurt, D., Endler, C., et al. (2023) · European Radiology · doi:10.1007/s00330-023-09864-x · Cited by 12
“This promotes steatogen-esis due to a decrease in the mitochondrial oxidation of fatty acids [22].”
Background
Association between Impaired Ketogenesis and Metabolic-Associated Fatty Liver Disease
Bae, J., & Lee, B. (2023) · Biomolecules · doi:10.3390/biom13101506 · Cited by 12
Lipases are differentially regulated by hormones to maintain free fatty acid homeostasis for insect brain development
Li, Y.-X., Yan, Q., Liu, T., Wang, J., & Zhao, X. (2024) · BMC Biology · doi:10.1186/s12915-024-01973-3 · Cited by 13
“Dietary fat hydrolysis produces FFAs, which can provide energy through β-oxidation for body growth [37], and FFAs can also be re-esterified to form lipids for energy storage [38, 39].”
Background
Lipase‐Catalyzed Enantiomer Separation of 3‐Hydroxy‐4‐(tosyloxy)butanenitrile: Synthesis of (R)‐GABOB (=(3R)‐4‐Amino‐3‐hydroxybutanoic Acid) and (R)‐Carnitine Hydrochloride (=(2R)‐3‐Carboxy‐2‐hydroxy‐N,N,N‐trimethylpropan‐1‐aminium Chloride)
Kamal, Ä., Khanna, G. B. R., & Tadiparthi, K. (2007) · Helvetica Chimica Acta · doi:10.1002/hlca.200790180 · Cited by 12
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Lee, H.-J., Chung, M., Kim, D., et al. (2009) · Journal of the Korean Society of Food Science and Nutrition · doi:10.3746/jkfn.2009.38.11.1516 · Cited by 12
“그러나 ACS를 활성화시킨 소재 는 CAT 외에 다른 효소들을 활성화시켜 지방 산화를 유도 할 수 있을 가능성이 있다(35,36).”
Changes in cardiac energy metabolic pathways in overweighed rats fed a high-fat diet
Modrego, J., Heras, N. D. L., Zamorano‐León, J. J., Mateos‐Cáceres, P. J., Martín‐Fernández, B., Valero‐Muñoz, M., Lahera, V., & López-Farré, A. J. (2012) · European Journal of Nutrition · doi:10.1007/s00394-012-0392-7 · Cited by 12
“the level of fatty acid uptake by mitochondria through CPTI, which transfers fatty acid from acyl-coenzyme A to long-chain acylcarnitine, that then it is transported into mitochondria [15, 16].”
Background
Topology of Hepatic Mitochondrial Carnitine Palmitoyltransferase I
Kashfi, K., & Cook, G. A. (2006) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-46818-2_3 · Cited by 13
Comparative study on the kinetic behaviour of carnitine palmitoyltransferase I between Javelin gobySynechogobius hasta(carnivorous) and grass carpCtenopharyngodon idella(herbirovous)
Zheng, J., Hu, W., Luo, Z., Zhao, Y., Zhu, Q., & Li, X.-D. (2013) · Aquaculture Nutrition · doi:10.1111/anu.12014 · Cited by 12
Momilactone B Inhibits Ketosis In Vitro by Regulating the ANGPTL3-LPL Pathway and Inhibiting HMGCS2
Kang, D. Y., Sp, N., Darvin, P., et al. (2016) · Animal Biotechnology · doi:10.1080/10495398.2016.1252769 · Cited by 12
“During fasting (glucose starvation), hepatic ketogenesis is rapidly elevated (17, 18).”
Background
Triglycerides Revisited to the Serial
Viecili, P. R. N., da Silva, B., Hirsch, G. E., Porto, F. G., Parisi, M. M., Castanho, A. R., Wender, M., & Klafke, J. Z. (2017) · Advances in clinical chemistry · doi:10.1016/bs.acc.2016.11.001 · Cited by 14
Acute Exercise Stimulates Carnitine Biosynthesis and OCTN2 Expression in Mouse Kidney
Broderick, T. L., Cusimano, F. A., Carlson, C., et al. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000478737 · Cited by 12
AMP-activated protein kinase protects against anoxia in Drosophila melanogaster
Evans, J. J., Xiao, C., & Robertson, R. M. (2017) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2017.09.006 · Cited by 12
Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State
Umpierrez, G. E. (2018) · Endocrinology · doi:10.1007/978-3-319-44433-8_21 · Cited by 12
Mitochondrial, but not peroxisomal, β-oxidation of fatty acids is conserved in coenzyme A-Deficient rat liver
Youssef, J., Song, W. O., & Badr, M. Z. (1997) · Molecular and Cellular Biochemistry · doi:10.1023/a:1006877021617 · Cited by 12
“This effect is not a result of body weight loss observed in CoA-deficient rats, since food deprivation is known to enhance rather than inhibit mitochondrial β-oxidation [29] and to also stimulate peroxisomal β-oxidation [19].”
Background
Mitochondrial disorders in chagasic cardiomyopathy
Nisha, G. (2005) · Frontiers in bioscience · doi:10.2741/1624 · Cited by 12
Central nervous system disorders and possible brain type carnitine palmitoyltransferase II deficiency
Ohtani, Y., Tomoda, A., Miike, T., et al. (1994) · Brain and Development · doi:10.1016/0387-7604(94)90051-5 · Cited by 12
MALIGNANT SOMATOSTATINOMA PRESENTING WITH DIABETIC KETOACIDOSIS
Jackson, J. A., Raju, B., FACHNIE, J. D., et al. (1987) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1987.tb00817.x · Cited by 12
Nutritional Effects of Randomly Interesterified and Physically Mixed Oils Containing Medium-chain Fatty Acids on Rats.
NOGUCHI, O., SHIMADA, H., KUBOTA, F., TSUJI, H., & AOYAMA, T. (2002) · Journal of Oleo Science · doi:10.5650/jos.51.699 · Cited by 12
“中鎖脂肪酸は,一般に炭素数が8から 10の脂肪酸を指し,通常の食用油に含まれる長鎖脂肪酸とは異なる経路で吸収される(1)。すなわち中鎖脂肪酸は,胃リパーゼで速やかに加水分解され,胆汁酸ミセルに溶解することなく小腸上皮細胞に吸収される。吸収後は門脈を経て肝臓に取り込まれ,肝細胞のミトコンドリアで b 酸化を受けてエネルギー代謝に利用される。このため中鎖脂肪酸は,体脂肪として蓄積され難いと言われている(2)。この他にもトリアシルグリセロール, コレステロールなどの脂質代謝に及ぼす影響,インシュリン,グルコースなどの糖質代謝に及ぼす影響, 窒素平衡などアミノ酸代謝やタンパク質代謝に及ぼす影響等,種々の生理作用が知られ…”
Kinetics of Medium‐Chain Triglycerides and Free Fatty Acids in Healthy Volunteers and Surgically Stressed Patients
Gaetano, A. D., Castagneto, M., Mingrone, G., et al. (1994) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607194018002134 · Cited by 12
Cloning, sequencing and heterologous expression of a cDNA encoding pigeon liver carnitine acetyltransferase
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Changes in serum lipoproteins in humans following the infusion of a fat emulsion containing medium‐ and long‐chain triglycerides
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Untitled work
Price (1999) · doi:10.1002/1531-8249(199903)45:3

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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