Metabolic flux between organs measured by arteriovenous metabolite gradients
0
조회
0
다운로드
1
인용
0
참고문헌
초록
Mammalian organs convert dietary nutrients into circulating metabolites and share them to maintain whole-body metabolic homeostasis. While the concentrations of circulating metabolites have been frequently measured in a variety of pathophysiological conditions, the exchange flux of circulating metabolites between organs is not easily measurable due to technical difficulties. Isotope tracing is useful for measuring such fluxes for a metabolite of interest, but the shuffling of isotopic atoms between metabolites requires mathematical modeling. Arteriovenous metabolite gradient measurements can complement isotope tracing to infer organ-specific net fluxes of many metabolites simultaneously. Here, we review the historical development of arteriovenous measurements and discuss their advantages and limitations with key example studies that have revealed metabolite exchange flux between organs in diverse pathophysiological contexts.
Abstract
Mammalian organs convert dietary nutrients into circulating metabolites and share them to maintain whole-body metabolic homeostasis. While the concentrations of circulating metabolites have been frequently measured in a variety of pathophysiological conditions, the exchange flux of circulating metabolites between organs is not easily measurable due to technical difficulties. Isotope tracing is useful for measuring such fluxes for a metabolite of interest, but the shuffling of isotopic atoms between metabolites requires mathematical modeling. Arteriovenous metabolite gradient measurements can complement isotope tracing to infer organ-specific net fluxes of many metabolites simultaneously. Here, we review the historical development of arteriovenous measurements and discuss their advantages and limitations with key example studies that have revealed metabolite exchange flux between organs in diverse pathophysiological contexts.
참고문헌 (126)
- Mulleder, M., "Functional metabolomics describes the yeast biosynthetic regulome", Cell, 167, pp.553~565.e512 (2016)
- You, C., "Coordination of bacterial proteome with metabolism by cyclic AMP signalling", Nature, 500, pp.301~306 (2013)
- Smith, R. L., "Metabolic flexibility as an adaptation to energy resources and requirements in health and disease", Endocr. Rev, 39, pp.489~517 (2018)
- Rinschen, M. M., "Identification of bioactive metabolites using activity metabolomics", Nat. Rev. Mol. Cell Biol, 20, pp.353~367 (2019)
- Robey, R. B., "Metabolic reprogramming and dysregulated metabolism:Cause, consequence and", or enabler of environmental carcinogenesis, 2015, pp.36, S203~S231
- Jang, C., "Metabolomics and tsotope tracing", Cell, 173, pp.822~837 (2018)
- Bartman, C. R., "Quantitative flux analysis in mammals", Nat. Metab, 3, pp.896~908 (2021)
- Fernandez-Garcia, J., "Stable isotopes for tracing mammalian-cell metabolism in vivo", Trends Biochem. Sci, 45, pp.185~201 (2020)
- Faubert, B., "Stable isotope tracing to assess tumor metabolism in vivo", Nat. Protoc, 16, pp.5123~5145 (2021)
- Faubert, B., "Lactate metabolism in human lung tumors", Cell, 171, pp.358~371.e359 (2017)
- Hui, S., "Glucose feeds the TCA cycle via circulating lactate", Nature, 551, pp.115~118 (2017)
- Hui, S., "Quantitative fluxomics of circulating metabolites", Cell Metab, 32, pp.676~688.e674 (2020)
- Neinast, "Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids", Cell Metab, 29, pp.417~429.e414 (2019)
- Tavoni, S. K., "Lactate flux and gluconeogenesis in fasting, weaned northern elephant seals(Mirounga angustirostris)", J. Comp. Physiol. B, 183, pp.537~546 (2013)
- Stanley, W. C., "Lactate extraction during net lactate release in legs of humans during exercise", J. Appl. Physiol, 60, pp.1116~1120 (1986)
- Weber, J. M., "Lactate kinetics in exercising thoroughbred horses—Regulation of turnover rate in plasma", Am. J. Physiol, 253, pp.R896~R903 (1987)
- Li, X., "Circulating metabolite homeostasis achieved through mass action", Nat. Metab, 4, pp.141~152 (2022)
- Jang, C., "The small intestine converts dietary fructose into glucose and organic acids", Cell Metab, 27, pp.351~361.e353 (2018)
- Lecoultre, V., "Fructose and glucose co-ingestion during prolonged exercise increases lactate and glucose fluxes and oxidation compared with an equimolar intake of glucose", Am. J. Clin. Nutr, 92, pp.1071~1079 (2010)
- Ahlborg, G., "Splanchnic and muscle fructose metabolism during and after exercise", J. Appl. Physiol, 69, pp.1244~1251 (1990)
- Felig, P., "Alanine: Key role in gluconeogenesis", Science, 167, pp.1003~1004 (1970)
- Schwalm, J. W., "Blood metabolite interrelationships and changes in mammary gland metabolism during subclinical ketosis", J. Dairy. Sci, 55, pp.58~64 (1972)
- Maas, J. W., "The determination of a brain arteriovenous difference for 3-methoxy-4-hydroxyphenethyleneglycol(MHPG)", Brain Res, 118, pp.167~173 (1976)
- de Jong, J. W., "Myocardial nucleoside and carbohydrate metabolism and hemodynamics during partial occlusion and reperfusion of pig coronary artery", J. Mol. Cell. Cardiol, 9, pp.297~312 (1977)
- Broad, T. E., "Arteriovenous changes in the concentration of glutamine and other metabolites across the Rumen of Sheep", Can. J. Anim. Sci, 60, pp.59~64 (1980)
- Ivanisevic, J., "Arteriovenous blood metabolomics : A readout of intra-tissue metabostasis", Sci. Rep, 5, pp.12757~ (2015)
- Jang, C., "Metabolite exchange between mammalian organs quantified in pigs", Cell Metab, 30, pp.594~606.e593 (2019)
- Cori, G. T., "Glucose-6-phosphatase of the liver in glycogen storage disease", J. Biol. Chem, 199, pp.661~667 (1952)
- Felig, P., "Glutamine and glutamate metabolism in normal and diabetic subjects", Diabetes, 22, pp.573~576 (1973)
- Aoki, T. T., "Leucine meal increases glutamine and total nitrogen release from forearm muscle", J. Clin. Invest, 68, pp.1522~1528 (1981)
- O'Donovan, S. D., "A computational model of postprandial adipose tissue lipid metabolism derived using human arteriovenous stable isotope tracer data", PLoS Comput. Biol, 15, pp.e1007400~ (2019)
- Murashige, D., "Comprehensive quantification of fuel use by the failing and nonfailing human heart", Science, 370, pp.364~368 (2020)
- Harms, C. A., "Respiratory muscle work compromises leg blood flow during maximal exercise", J. Appl. Physiol, 82, pp.1573~1583 (1997)
- Sieber, C., "Regulation of postprandial mesenteric blood flow in humans : evidence for a cholinergic nervous reflex", Gut, 32, pp.361~366 (1991)
- Lopez-Soriano, F. J., "Amino acid and glucose uptake by rat brown adipose tissue. Effect of cold-exposure and acclimation", Biochem. J, 252, pp.843~849 (1988)
- Calafiore, A. M., "Minimally invasive mammary artery Doppler flow velocity evaluation in minimally invasive coronary operations", Ann. Thorac. Surg, 66, pp.1236~1241 (1998)
- Laustsen, J., "Validation of a new transit time ultrasound flowmeter in man", Eur. J. Vasc. Endovasc. Surg, 12, pp.91~96 (1996)
- Beldi, G., "Transit time flow measurement : Experimental validation and comparison of three different systems", Ann. Thorac. Surg, 70, pp.212~217 (2000)
- Domenech, R. J., "Total and regional coronary blood flow measured by radioactive microspheres in conscious and anesthetized dogs", Circ. Res, 25, pp.581~596 (1969)
- Zapol, W. M., "Regional blood flow during simulated diving in the conscious Weddell seal", J. Appl. Physiol. Respir. Environ. Exerc. Physiol, 47, pp.968~973 (1979)
- Van Oosterhout, M. F., "Fluorescent microspheres are superior to radioactive microspheres in chronic blood flow measurements", Am. J. Physiol, 275, pp.H110~H115 (1998)
- Ten Have, G. A., "Simultaneous measurement of metabolic flux in portally-drained viscera, liver, spleen, kidney, and hindquarter in the conscious pig", Lab. Anim, 30, pp.347~358 (1996)
- Owen, O. E., "Brain metabolism during fasting", J. Clin. Invest, 46, pp.1589~1595 (1967)
- leucine as the tracer, "Clin. Sci", 1987, 241~246
- Bartlett, K., "Human forearm arteriovenous differences of carnitine, short-chain acylcarnitine, and long-chain acylcarnitine", Clin. Sci, 77, pp.413~416 (1989)
- Schooneman, M. G., "Transorgan fluxes in a porcine model reveal a central role for liver in acylcarnitine metabolism", Am. J. Physiol. Endocrinol. Metab, 309, pp.E256~E264 (2015)
- Windmueller, H. G., "Respiratory fuels and nitrogen metabolism in vivo in small intestine of fed rats. Quantitative importance of glutamine, glutamate, and aspartate", J. Biol. Chem, 255, pp.107~112 (1980)
- Garcia, R. A., "The splanchnic organs, liver, and kidney have unique roles in the metabolism of sulfur amino acids and their metabolites in rats", J. Nutr, 122, pp.1693~1701 (1992)
- Boisclair, Y. R., "Evaluation of the arteriovenous difference technique to simultaneously estimate protein synthesis and degradation in the hindlimb of fed and chronically underfed steers", J. Nutr, 123, pp.1076~1088 (1993)
- Klein, J., "Small rises in plasma choline reverse the negative arteriovenous difference of brain choline", J. Neurochem, 55, pp.1231~1236 (1990)
- Kowalski, T. J., "Rat adipose tissue amino acid metabolism in vivo as assessed by microdialysis and arteriovenous techniques", Am. J. Physiol, 273, pp.E613~E622 (1997)
- Stumvoll, M., "Human kidney and liver gluconeogenesis : Evidence for organ substrate selectivity", Am. J. Physiol, 274, pp.E817~E826 (1998)
- Meyer, C., "Role of human liver, kidney, and skeletal muscle in postprandial glucose homeostasis", Am. J. Physiol. Endocrinol. Metab, 282, pp.E419~E427 (2002)
- Schwalm, J. W., "Blood metabolite interrelationships and changes in mammary-gland metabolism during subclinical ketosis", J. Dairy Sci, 55, pp.58~64 (1972)
- Cant, J. P., "Mammary uptake of energy metabolites in dairy-cows fed fat and its relationship to milk protein depression", J. Dairy Sci, 76, pp.2254~2265 (1993)
- Poupin, N., "Arterio-venous metabolomics exploration reveals major changes across liver and intestine in the obese Yucatan minipig", Sci. Rep, 9, pp.12527~ (2019)
- Tremblay-Franco, M., "Postprandial NMR-based metabolic exchanges reflect impaired phenotypic flexibility across splanchnic organs in the Obese Yucatan mini-pig", Nutrients, 12, pp.2442~ (2020)
- Wahren, J., "Glucose metabolism during leg exercise in man", J. Clin. Invest, 50, pp.2715~2725 (1971)
- Gertz, E. W., "Myocardial substrate utilization during exercise in humans. Dual carbon-labeled carbohydrate isotope experiments", J. Clin. Invest, 82, pp.2017~2025 (1988)
- Bergman, B. C., "Active muscle and whole body lactate kinetics after endurance training in men", J. Appl. Physiol, 87, pp.1684~1696 (1999)
- van Hall, G., "Blood lactate is an important energy source for the human brain", J. Cereb. Blood. Flow. Metab, 29, pp.1121~1129 (2009)
- Johnson, M. L., "Transpulmonary pyruvate kinetics", Am. J. Physiol. Regul. Integr. Comp. Physiol, 301, pp.R769~R774 (2011)
- Hu, C., "Muscle-liver substrate fluxes in exercising humans and potential effects on hepatic metabolism", J. Clin. Endocrinol. Metab, 105, pp.1196~1209 (2020)
- Polakof, S., "Metabolic adaptations to HFHS overfeeding : How whole body and tissues postprandial metabolic flexibility adapt in Yucatan mini-pigs", Eur. J. Nutr, 57, pp.119~135 (2018)
- Polakof, S., "Time-course changes in circulating branched-chain amino acid levels and metabolism in obese Yucatan minipig", Nutrition, 50, pp.66~73 (2018)
- Martin, G., "Glutamine gluconeogenesis in the small intestine of 72 h-fasted adult rats is undetectable", Biochem. J, 401, pp.465~473 (2007)
- Brunengraber, D. Z., "Absence of intestinal gluconeogenesis in rats and dogs", Faseb J, 21, pp.A1073~A1073 (2007)
- Grill, V., "A comparison of brain glucose metabolism in diabetes as measured by positron emission tomography or by arteriovenous techniques", Ann. Med, 22, pp.171~176 (1990)
- van Hees, A. M., "Skeletal muscle fatty acid handling in insulin resistant men", Obesity, 19, pp.1350~1359 (2011)
- Jans, A., "PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity", Am. J. Clin. Nutr, 95, pp.825~836 (2012)
- Bing, R. J., "Metabolic studies on the human heart in vivo. I. Studies on carbohydrate metabolism of the human heart", Am. J. Med, 15, pp.284~296 (1953)
- Harris, P., "Lactate, pyruvate, glucose, and free fatty acid in mixed venous and arterial blood", J. Appl. Physiol, 18, pp.933~936 (1963)
- Voros, G., "Increased cardiac uptake of ketone bodies and free fatty acids in human heart failure and hypertrophic left ventricular remodeling", Circ. Heart Fail, 11, pp.e004953~ (2018)
- Pal, N., "Metabolic profiling of aortic stenosis and hypertrophic cardiomyopathy identifies mechanistic contrasts in substrate utilisation", bioRxiv, ~ (2019)
- Rhee, E. P., "A combined epidemiologic and metabolomic approach improves CKD prediction", J. Am. Soc. Nephrol, 24, pp.1330~1338 (2013)
- Rhee, E. P., "Metabolomics of chronic kidney disease progression: A casecontrol analysis in the chronic renal insufficiency cohort study", Am. J. Nephrol, 43, pp.366~374 (2016)
- Wijermars, L. G., "The hypoxanthine-xanthine oxidase axis is not involved in the initial phase of clinical transplantation-related ischemia-reperfusion injury", Am. J. Physiol. Ren. Physiol, 312, pp.F457~F464 (2017)
- Lindeman, J. H., "Results of an explorative clinical evaluation suggest immediate and persistent post-reperfusion metabolic paralysis drives kidney ischemia reperfusion injury", Kidney Int, 98, pp.1476~1488 (2020)
- Nosadini, R., "Carbohydrate and lipid metabolism in cirrhosis. Evidence that hepatic uptake of gluconeogenic precursors and of free fatty acids depends on effective hepatic flow", J. Clin. Endocrinol. Metab, 58, pp.1125~1132 (1984)
- Strauss, B., "Observations on a model of proliferative lung disease. I. Transpulmonary arteriovenous differences of lactate, pyruvate, and glucose", J. Clin. Invest, 49, pp.1305~1310 (1970)
- Morgan, M. A., "Artery-to-vein differences in nitric oxide metabolites are diminished in sepsis", Crit. Care. Med, 38, pp.1069~1077 (2010)
- Hawkins, R. A., "Research Methods in Neurochemistry" (1974), Springer
- Aquilonius, S. M., "The arteriovenous difference of choline across the brain of man", Brain. Res, 99, pp.430~433 (1975)
- Scremin, O. U., "Effects of hypoxia on choline exchange among organs", J. Neurochem, 59, pp.906~914 (1992)
- Jalloh, I., "Lactate uptake by the injured human brain: Evidence from an arteriovenous gradient and cerebral microdialysis study", J. Neurotrauma, 30, pp.2031~2037 (2013)
- Glenn, T. C., "Lactate: brain fuel in human traumatic brain injury: A comparison with normal healthy control subjects", J. Neurotrauma, 32, pp.820~832 (2015)
- Xiong, N., "Using arterial-venous analysis to characterize cancer metabolic consumption in patients", Nat. Commun, 11, pp.3169~ (2020)
- Tabata, H., "Comparison of effects of restraint, cage transportation, anaesthesia and repeated bleeding on plasma glucose levels between mice and rats", Lab. Anim, 32, pp.143~148 (1998)
- Young, R., "Perioperative fluid and electrolyte management in cardiac surgery : a review", J. Extra Corpor. Technol, 44, pp.P20~P26 (2012)
- Hubbard, L., "Low-radiation-dose stress myocardial perfusion measurement using first-pass analysis dynamic computed tomography : A preliminary investigation in a swine model", Invest. Radiol, 54, pp.774~780 (2019)
- Arepally, A., "Percutaneous MR imagingguided transvascular access of mesenteric venous system: Study in swine model", Radiology, 238, pp.113~118 (2006)
- Mahnken, A. H., "CT fluoroscopy-guided placement of inferior vena cava filters: Feasibility study in pigs", J. Vasc. Interv. Radiol, 22, pp.1531~1534 (2011)
- Omary, R. A., "MR imaging- versus conventional X-ray fluoroscopy-guided renal angioplasty in swine: Prospective randomized comparison", Radiology, 238, pp.489~496 (2006)
- Arepally, A., "Evaluation of MR", fluoroscopy-guided portosystemic shunt creation in a swine model, 2006, pp.17, 1165~1173
- Petersen, B., "Intravascular ultrasound-guided direct intrahepatic portacaval shunt: description of technique and technical refinements", J. Vasc. Interv. Radiol, 14, pp.21~32 (2003)
- Brooks, G. A., "Lactate in contemporary biology: A phoenix risen", J. Physiol, 600, pp.1229~1251 (2021)
- Evers, T. M. J., "Deciphering metabolic heterogeneity by single-cell analysis", Anal. Chem, 91, pp.13314~13323 (2019)
- Rappez, L., "SpaceM reveals metabolic states of single cells", Nat. Methods, 18, pp.799~805 (2021)
- Rubakhin, S. S., "Profiling metabolites and peptides in single cells", Nat. Methods, 8, pp.S20~S29 (2011)
- Ibanez, A. J., "Mass spectrometry-based metabolomics of single yeast cells", Proc. Natl Acad. Sci. USA, 110, pp.8790~8794 (2013)
- Taylor, M. J., "Spatially resolved mass spectrometry at the single cell : Recent innovations in proteomics and metabolomics", J. Am. Soc. Mass. Spectrom, 32, pp.872~894 (2021)
- Gine, R., "HERMES : A molecular-formula-oriented method to target the metabolome", Nat. Methods, 18, pp.1370~1376 (2021)
- Chen, L., "Metabolite discovery through global annotation of untargeted metabolomics data", Nat. Methods, 18, pp.1377~1385 (2021)
- Jolliffe, I. T., "Principal component analysis: A review and recent developments", Philos. Trans. A. Math. Phys. Eng. Sci, 374, pp.20150202~ (2016)
- Masuda, N., "Clustering coefficients for correlation networks", Front. Neuroinform, 12, pp.7~ (2018)
- Volkova, S., "Metabolic modelling as a framework for metabolomics data integration and analysis", Metabolites, 10, pp.303~ (2020)
- Deng, L., "Identifying significant metabolic pathways using multi-block partial least-squares analysis", J. Proteome Res, 19, pp.1965~1974 (2020)
- Ten Have, G. A. M., "Metabolic flux analysis of branched-chain amino and keto acids (BCAA, BCKA)and beta-hydroxy beta-methylbutyric acid across multiple organs in the pig", Am. J. Physiol. Endocrinol. Metab, 320, pp.E629~E640 (2021)
- Pethick, D. W., "Nutrient utilisation by the hindlimb of thoroughbred horses at rest", Equine Vet. J, 25, pp.41~44 (1993)
- Stallknecht, B., "Evaluation of the microdialysis technique in the dog fat pad", Am. J. Physiol, 276, pp.E588~E595 (1999)
- Paschen, U., "Serial blood sampling from the portal and hepatic vein in conscious unrestrained miniature pigs", Res. Exp. Med, 186, pp.87~92 (1986)
- Nichols, K., "Mammary gland utilization of amino acids and energy metabolites differs when dairy cow rations are isoenergetically supplemented with protein and fat", J. Dairy. Sci, 102, pp.1160~1175 (2019)
- Reeds, P. J., "Enteral glutamate is almost completely metabolized in first pass by the gastrointestinal tract of infant pigs", Am. J. Physiol, 270, pp.E413~E418 (1996)
- Cumpstey, A. F., "Pushing arterial-venous plasma biomarkers to new heights: A model for personalised redox metabolomics?", Redox Biol, 21, pp.101113~ (2019)
- Nielsen, T. T., "Leg and splanchnic arteriovenous differences of plasma citrate in exercising man", J. Appl. Physiol. Respir. Environ. Exerc. Physiol, 46, pp.120~127 (1979)
- Vink, R. G., "Adipose tissue meal-derived fatty acid uptake before and after diet-induced weight loss in adults with overweight and Obesity", Obesity, 25, pp.1391~1399 (2017)
- Isabelle, S. A., "Profound changes in net energy and nitrogen metabolites fluxes within the saplanchnic area during overfeeding of Yucatan mini pigs that remain euglycemic", Nutrients, 11, pp.434~ (2019)
- Goossens, G. H., "Altered skeletal muscle fatty acid handling in subjects with impaired glucose tolerance as compared to impaired fasting glucose", Nutrients, 8, pp.164~ (2016)
- Wijermars, L. G., "Defective postreperfusion metabolic recovery directly associates with incident delayed graft function", Kidney Int, 90, pp.181~191 (2016)
- Fowden, A. L., "The effect of pancreatectomy on the uptake of metabolites by the sheep fetus", Q. J. Exp. Physiol, 71, pp.67~78 (1986)
- Stjernstrom, H., "The influence of abdominal surgical trauma upon the turnover of some blood-borne energy metabolites in the human leg", JPEN J. Parenter. Enter. Nutr, 5, pp.207~214 (1981)
- Laptook, A. R., "Alterations in cerebral blood flow and phosphorylated metabolites in piglets during and after partial ischemia", Pediatr. Res, 23, pp.206~211 (1988)
- Gaab, M., "Comparison of the effects of surgical decompression and resection of local edema in the therapy of experimental brain trauma. Investigation of ICP, EEG, and cerebral metabolism in cats", Childs Brain, 5, pp.484~498 (1979)
- Madsen, P. L., "Cerebral oxygen", glucose ratio is low during sensory stimulation and rises above normal during recovery : Excess glucose consumption during stimulation is not accounted for by lactate efflux from or accumulation in brain tissue, 1999, pp.19, 393~400
- Peebles, K. C., "Human cerebral arteriovenous vasoactive exchange during alterations in arterial blood gases", J. Appl. Physiol, 105, pp.1060~1068 (2008)
- Wolahan, S. M., "Novel metabolomic comparison of arterial and jugular venous blood in severe adult traumatic brain injury patients and the impact of pentobarbital infusion", J. Neurotrauma, 36, pp.212~221 (2019)
